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City of Huntington Beach APPROVED FOR ADOPTION
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File #: 25-725 MEETING DATE: 9/16/2025
REQUEST FOR CITY COUNCIL ACTION
SUBMITTED TO: Honorable Mayor and City Council Members
SUBMITTED BY: Travis Hopkins, City Manager
VIA: Eric Parra, Chief of Police
PREPARED BY: Shannon Levin, Council Policy Analyst and Kevin Johnson, Captain
Subject:
Adopt Ordinance No. 4339 Prohibiting the Sale, Distribution and Possession of Kratom -
Approved for Introduction September 2, 2025, by a vote of 7-0
Statement of Issue:
At the request of Council Woman Gracey Van Der Mark, the Huntington Beach City Council, at its
August 19, 2025, meeting, directed staff to prepare an ordinance prohibiting the sale and distribution
of Kratom within the City. The City Council voted unanimously in support of bringing the ordinance
forward for consideration.
Financial Impact:
Not applicable.
Recommended Action:
Adopt Ordinance No. 4339, "An Ordinance of the City Council of the City of Huntington Beach
Amending the Huntington Beach Municipal Code by Adding New Chapter 9.92 Thereof Prohibiting
the Sale, Distribution and Possession of Kratom."
Alternative Action(s):
Do not approve the recommended action and direct staff accordingly.
Analysis:
Kratom is a tropical tree native to Southeast Asia. Its leaves contain psychoactive compounds,
including mitragynine and 7-hydroxymitragynine, which can produce stimulant effects at low doses
and sedative effects at high doses. According to the Drug Enforcement Administration (DEA) and the
National Institutes of Health (NIH), Kratom use has been associated with a range of adverse health
impacts, including psychotic symptoms, dependence, and numerous side effects such as nausea,
vomiting, sweating, constipation, tachycardia, seizures, hallucinations, and hepatotoxicity.
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File #: 25-725 MEETING DATE: 9/16/2025
Although Kratom is often marketed for relief of pain, anxiety, opioid withdrawal, and fatigue, there are
no FDA-approved medical uses for the substance. The FDA continues to monitor reports of adverse
events, and current data suggests Kratom's opioid-like properties may expose users to risks of
addiction, abuse, and dependence.
Several states and local jurisdictions have prohibited the sale or possession of Kratom, including
Alabama, Arkansas, Indiana, Rhode Island, Vermont, Wisconsin, the City of San Diego (2016),
Newport Beach (2025), and the County of Orange (2025). Kratom is not currently regulated at the
federal level, nor is it prohibited statewide in California.
The intention of this ordinance is to prohibit the sale, distribution, or possession of kratom and other
products within the City of Huntington Beach that contain more than 2% of 7-hydroxymitraginyne in
the alkaloid fraction, recognizing significant health risks associated with elevated concentrations of
the alkaloid; prohibit the sale of any kratom product that is adulterated with synthesized or semi-
synthesized kratom alkaloids or kratom constituents; and prohibit the sale or distribution of kratom
product to a person under 21 years of age.
Penalties for those who violate HBMC §9.92.030 will be guilty of a misdemeanor and may be fined up
to $1000 or be imprisoned in County Jail for not more than six months; and if applicable the
Huntington Beach Business License may be revoked pursuant to HBMC §5.08.300.
Environmental Status:
This action is not subject to the California Environmental Quality Act (CEQA) pursuant to Sections
15060(c)(2) (the activity will not result in a direct or reasonably foreseeable indirect physical change
in the environment) and 15060(c)(3) (the activity is not a project as defined in Section 15378) of the
CEQA Guidelines, California Code of Regulations, Title 14, Chapter 3, because it has no potential for
resulting in physical change to the environment, directly or indirectly.
Strategic Plan Goal:
Non Applicable -Administrative Item
Attachment(s):
1.Ordinance No. 4339
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ORDINANCE NO. 4339
AN ORDINANCE OF THE CITY COUNCIL OF THE CITY OF HUNTINGTON BEACH
AMENDING THE HUNTINGTON BEACH MUNICIPAL CODE BY ADDING NEW
CHAPTER 9.92 THEREOF PROHIBITING THE SALE, DISTRIBUTION AND POSSESSION
OF KRATOM
The City Council of the City of Huntington Beach does hereby ordain as follows:
SECTION 1. WHEREAS, it is the intent of the City Council to prohibit the sale,
distribution, or possession of kratom and other products within the City of Huntington Beach that
contain more than 2% of 7-hydroxymitragynine in the alkaloid fraction, recognizing the
significant health risks associated with elevated concentrations of this alkaloid; and
Kratom (Mitragyna speciosa) is a tropical tree native to Southeast Asia, and its leaves are
often consumed in powdered or extract form for their stimulant and sedative effects; and
The active compounds in kratom include mitragynine and 7-hydroxymitragynine. While
mitragynine is present in higher concentrations, 7-hydroxymitragynine is more potent and is
largely responsible for the stronger pain-relieving, sedative, and euphoric effects; and
7-hydroxymitragynine binds to opioid receptors in the brain and has been shown to have
euphoric and mood-enhancing effects, particularly at higher doses, which can increase its appeal
for recreational use; and
7-hydroxymitragynine is believed to be more potent than morphine in terms of pain
relief. Research has shown that it binds to opioid receptors in the brain with greater affinity than
morphine, making it significantly more powerful in relieving pain. This greater potency raises
significant concerns about its safety profile, especially regarding the potential for addiction,
overdose, and adverse physical and psychological effects, including nausea, vomiting, and
potential psychosis. These risks are compounded when products contain higher concentrations of
7-hydroxymitragynine; and
Scientific research and health advisories have raised concerns over the safety of kratom
products, particularly those with higher concentrations of 7-hydroxymitragynine, which may
increase the potential for abuse and harm to public health; and
Several cities in California have taken steps to regulate or ban kratom products,
recognizing the need to protect public safety, especially among vulnerable populations. For
example,Newport Beach, San Diego, and Oceanside have all enacted a complete ban on the sale,
distribution, and possession of all kratom products - irrespective of the concentration of 7-
hydroxymitragynine content; and
The U.S. Food and Drug Administration has issued several warning letters to various
companies for illegally marketing products containing enhanced levels of 7-
hydroxymitragynine, culminating in a formal request to the Drug Enforcement Administration
25-16974/387632
ORDINANCE NO. 4339
(DEA) on July 29, 2025, to place 7-hydroxymitragynine products on the controlled substance
list; and
The City Council is committed to safeguarding the health and well-being of its residents
by ensuring that products available for sale do not pose undue health risks; and
The City Council wishes to restrict the sale and distribution of kratom and other products
containing more than 2% of 7-hydroxymitragynine in the alkaloid fraction, thereby reducing
potential risks to public health and safety.
SECTION 2. New Chapter 9.92 is added to the Huntington Beach Municipal Code to
read as follows:
"Chapter 9.92 SALE, DISTRIBUTION, AND POSSESSION OF KRATOM
PROHIBITED
§ 9.92.010 Purpose and Intent.
§ 9.92.020 Definitions.
§ 9.92.030 Sale, distribution and possession of kratom prohibited.
§ 9.92.040 Violations and Penalties.
§ 9.92.050 Severability.
§ 9.92.010 Purpose and Intent.
This article is enacted pursuant to the City's plenary police powers to protect
public safety, health and welfare. The express purpose of this article is to protect
public health and safety by regulating access to kratom and other products
containing more than 2% of 7- hydroxymitragynine in the alkaloid fraction.
§ 9.92.020 Definitions.
For purposes of this article, the following definitions apply.
(a) "Attractive to children" means any of the following:
(1) Use of images that are attractive to children, including, but not limited
to, images of any of the following, except as part of required health warnings:
(A) Cartoons, toys, or robots.
(B) Any real or fictional humans.
(C) Fictional animals or creatures.
(D) Fruits or vegetables, except when used to accurately describe
ingredients or flavors contained in a product.
2
ORDINANCE NO. 4339
(2) Likeness to images, characters, or phrases that are popularly used to
advertise to children.
(3) Imitation of candy packaging or labeling, or other packaging and
labeling of cereals, sweets, chips, or other food products typically marketed to
children.
(4) The terms "candy" or "candies" or variants in spelling such as "kandy"
or "kandee.
(5) Brand names or close imitations of brand names of candies, cereals,
sweets, chips, or other food products typically marketed to children.
(6) Any other image or packaging that is easily confused with
commercially available foods that do not contain lcratom and are typically
marketed to children.
(7) Any other packaging used that is attractive to children considering all
relevant facts and circumstances.
(b) "Kratom leaf' means the leaf of the kratom plant, also known as mitragyna
speciosa, any form.
(c) "Kratom leaf extract" means the material obtained by extraction of kratom
leaves by any means.
(d) "Kratom product" means a product consisting of any part of a leaf of the plant
Mitragyna speciosa in fresh, dehydrated, or dried form; or a kratom extract, or any
product that contains any kratom alkaloid or metabolite.
(e) "Total kratom alkaloids" means the sum of mitragynine, speciociliatine,
speciogynine, paynantheine, and 7-hydroxymitragynine in a kratom product.
(f) "Synthesized" means an alkaloid or alkaloid derivative that has been created
by chemical synthesis or biosynthetic means (including but not limited to;
fermentation, recombinant techniques, yeast derived, enzymatic techniques),
rather than traditional food preparation techniques such as heating or extracting. It
also includes alkaloids that has been further exposed to chemicals or processes
that would confer a structural change in the alkaloids contained within the extract.
§ 9.92.030 Sale, distribution and possession of kratom prohibited.
(a) Except as otherwise authorized by law, an individual, business, or other entity
shall not sell, attempt to sell, offer, provide, or distribute a kratom product to a
person under 21 years of age.
3
ORDINANCE NO. 4339
(b) Except as otherwise authorized by law, an individual, business, or other entity
shall not sell, attempt to sell, offer, provide, or distribute any product with a level
of 7-hydroxymitragynine that is greater than 2 percent of the total alkaloids in the
product.
(c) Except as otherwise authorized by law, an individual, business, or other entity
shall not sell, attempt to sell, offer, provide, or distribute a kratom product that is
attractive to children.
(d) Any individual, business, or other entity that sells, attempts to sell, offers,
provides, or distributes a kratom product shall conduct age-verification to ensure
compliance with subdivision (a).
(e)No person or entity shall offer for sale any kratom product that contains or is
adulterated with synthesized or semi-synthesized kratom alkaloids or kratom
constituents.
§ 9.92.040 Violations and Penalties.
Any person who violates section § 9.92.030 is guilty of a misdemeanor and upon
conviction thereof may be punished by a fine of not more than one thousand
dollars ($1,000.00) or by imprisonment in the County Jail for a period of not more
than six (6) months or by both such fine and imprisonment. This section shall not
serve to limit any other legal remedies or actions that the City may have to
address violations of§ 9.92.030. A violation of§ 9.92.030 is grounds for a
revocation of a business license, if applicable, pursuant to § 5.08.300 of the
Huntington Beach Municipal Code.
§ 9.92.050 Severability.
If any section, paragraph, sentence, clause, phrase or portion of this article is held
invalid or unconstitutional by any court of competent jurisdiction, such portion
shall be deemed severable and such holding shall not affect the validity of the
remaining portions hereof. The City Council hereby declares that it would have
adopted this article irrespective of the invalidity of any particular portion thereof
and intends that the invalid portions should be severed, and the balance of the
article be enforced.
SECTION 3. This ordinance shall become effective 30 days after its adoption.
4
ORDINANCE NO. 4339
PASSED AND ADOPTED by the City Council of the City of Huntington Beach at a
regular meeting thereof held one .eyh}yt- I1Q2025
Mayor
REVIEWED AND APPROVED: TTEST.
ana er M CityClerk
g
INIT. • ED a,ND APP" OVED: APPROVED AS TO FORM:
•
Police Chief City Attorney ®�
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5
Ord. No. 4339
STATE OF CALIFORNIA )
COUNTY OF ORANGE ) ss:
CITY OF HUNTINGTON BEACH )
I, LISA LANE BARNES,the duly elected, qualified City Clerk of the
City of Huntington Beach, and ex-officio Clerk of the City Council of said City, do
hereby certify that the whole number of members of the City Council of the City of
Huntington Beach is seven; that the foregoing ordinance was read to said City Council at
a Regular meeting thereof held on September 2, 2025, and was again read to said City
Council at a Regular meeting thereof held on September 16,2025, and was passed and
adopted by the affirmative vote of at least a majority of all the members of said City
Council.
AYES: Twining, Kennedy, McKeon,Bums,Van Der Mark, Gruel, Williams
NOES: None
ABSENT: None
ABSTAIN: None
I,Lisa Lane Barnes,CITY CLERK of the City of Huntington
Beach and ex-officio Clerk of the City Council,do hereby
certify that a synopsis of this ordinance has been published in
the Huntington Beach Wave on September 25,2025. OL'
to `�/if//tiar. •
In accordance with the City Charter of said City.
- Lisa ane Barnes, City Clerk City Clerk and ex-officio Clerk
Senior Deputy City Clerk of the City Council of the City
of Huntington Beach, California
From: Jared Beam
To: suoolementalcomm( surfcity-hb.orq
Subject: Public Comment on Agenda Item#25-725/Ordinance 4339
Date: Friday,September 12,2025 2:52:48 AM
You don't often get email fromjaredbeam3@gmail.com. I earn why this is important
Dear City Council,
I urge you to oppose the banning of kratom and its alkaloids (Agenda Item#25-725,
Ordinance 4339). The current spread of misinformation is being driven by lobbying interests,
not genuine public health concerns.
I am rebutting the falsehoods stated as fact during the last hearing. There are zero confirmed
overdoses from 7-hydroxymitragynine (7-OH) alone despite an estimated over 500 million
doses taken worldwide. Claims that children can simply walk into smoke shops and buy these
products are false, as minors are not allowed to purchase products there. The assertion that 7-
OH can be bought on Amazon is also untrue.
Comparing 7-OH to fentanyl is misleading. The real "new fentanyls" are synthetic opioids
called"zenes,"which can be up to 20 times stronger than fentanyl. 7-OH is a natural alkaloid
from the kratom plant, used safely for hundreds of years, and it is saving lives, not taking
them.
I use 7-OH to live a better life and stay safe from dangerous synthetic opioids. It has given me
back a normal life I never thought I'd have again. Every day, it helps people avoid fentanyl,
xylazine, and the dangerous synthetics driving the overdose crisis, while providing a safe
option for chronic pain patients left without effective relief.
Hundreds of millions of safe doses and countless life-saving stories confirm 7-OH's safety.
False claims from the last hearing are slanderous and dangerous. Acting on them would strip
people of safe harm reduction options while leaving far more dangerous drugs on the streets.
Thank you for your time and consideration. I hope you will protect access to safe, natural
harm reduction tools.
Respectfully,
Jared Beam
SUPPLEMENTAL
COMMUNICATION
Meeting Date: 09/16/2025
Agenda Item No. 13 (25-725)
From: Derek F
To: 5uoolementalcomm(@surfcity-hb.org
Subject: Agenda item 25-725 and ordinance 4339
Date: Friday,September 12,2025 5:24:31 PM
1 You don't often get email from derekpfaria@gmail.com.1 earn why this is imoortant
To whom it may concern,
My name is Derek Faria, I live in Weymouth Massachusetts,and have family and friends in
Huntington Beach. I'm writing to respectfully urge you not to support a ban on kratom and or
it's alkaloids like 7oh.
I understand the intent to protect public health,but it's quiet the contrary. I have serious
concerns about the consequences this ban could have for responsible adult users like myself. I
use 7OH products daily and have no abnormal issues or health concerns whatsoever. Kratom
and 7OH make my life better and allow me to get through the day without harsh prescription
medicine. I use it for a plethora of reasons, including anxiety management,pain reduction,and
overall sense of well-being.
I support regulation to ensure safety and product purity(such as age limits,manufacturing
standards,tamper proof packaging, etc), but I oppose a ban without fair hearings or scientific
discussion. There is so much misinformation on 7-hydroxymitraganine (7OH as it's marketed).
In fact, as kratom and 7oh have grown,overdoses nationally have began to decline for the first
time in YEARS. This plant-based alkaloid is literally saving lives of people that would
otherwise be using harsh and harmful street drugs such as fentnyl.A sudden ban of 7OH,I
fear,will cause many to resort back to street drugs and lose their lives.
Please consider the voices of everyday citizens who are using 7OH responsibly and benefiting
from it. I would urge and appreciate the opportunity for public input before an outright ban.
PLEASE gather input and evidence before supporting a ban. I've linked an independent study
from the group HART(Holistic Alternative Recovery Trust), showing 7-hydroxymitraganine,
and it's parent plant kratom both as being safe. If 7OH was a deadly substance I promise you I
would not be alive right now. It's quite the opposite,without it my quality of life would suffer,
and I speak for so many of us in the community.
https://www.reuters.comLpress-releases/experts-call-for-evidence-based-7oh-regulation-2025-
07-07/
Please see the article above. I urge the you to do your due diligence and reach out to groups
like HART to get the facts.
Respectfully,
Derek Faria
From: Pan Phan
To: suoolementalcomm(asurfcity-hb.orq
Subject: Item#25 and Ordinance 4339
Date: Friday,September 12,2025 8:20:03 PM
You don't often get email from danphan323@gmail.com.1 earn why this is important
To Whom It May Concern,
My name is Daniel Phan and I am writing to you to express my strong opposition to the
scheduling or banning of kratom, or any of its alkaloids, including 7oh.
These substances saves lives. I myself have used kratom to get off of much harsher, deadly
substances like fentanyl. Kratom/7oh do not represent a public health risk(Henningfield et al.
2022), and as partial agonists, do not cause dangerous respiratory depression (Kumar et al.
2018). Where are the bodies that would justify a ban? Please listen to the science and not the
fear mongering born of corporate interest: kratom leaf vendors seeking to regain market share
lost to 7oh.
If you ban kratom or 7oh,people WILL die. They will go back to deadly street opioids, or end
their own lives rather than live in debilitating pain. You would be taking away a life saving
tool, with devastating consequences; it would be an unacceptable blunder of public health
policy.
I urge you to look at the facts and listen to what the actual scientists are saying, such as those
at HART. Kratom and 7oh are safe. They save lives. Please do your duty to the greater good
of the American people.
Thank you,
Daniel Phan
Henningfield et al. (2022) explains why 7-OH doesn't meet ban criteria—and that banning it
could even increase overdose deaths by removing a safer option.
PMC8860177
Kumar et al. (2018)and Kruegel et al. (2019) both show 7-OH interacts with opioid receptors
in a safer, more targeted way—meaning less risk of overdose.
Kumar 2018
Kruegel 2019
From: 5ouochair:
To: suoolementalcommCalsurfcity-hb.org
Subject: Agenda Item#25-725/Ordinance 4339
Date: Saturday,September 13,2025 11:03:38 AM
You don't often get email from soupchain@proton.me.I earn why this is important
Dear City Council,
I am writing to implore you: please do not ban 7Oh and kratom. I am from Long Beach and
now live in Huntington Beach, and I take kratom everyday three times a day (for the past 8
years), and use 7Oh for the really bad pain flares. If you make kratom/7oh illegal you will put
me in a situation where I will not be able to function. I will lose my job and end up in a really
bad situation.
I have severe spinal stenosis, including multi-level foraminal stenosis in my lumbar,thoracic,
and cervical vertebrae. This is a genetic condition, I was born this way and I have dealt with
extreme and chronic pain since I was in my teens. I am 48 years old now. I have a family that
loves me and counts on me, and they all know I take kratom/7oh daily. I consider them
medications and I am literally scared to death to face life without those two medications. My
condition is so severe that I will not be able to work and support my family.
Why not traditional medicine and opioid medications? I have been off and on in pain
management all my life. I have tried everything from injections (imagine monthly procedures),
to neural ablation (nerve burning),to opioid medications. They work for a very short period
and then they literally stop working. Or, in the case of opioids, I end up reaching the ceiling
dose and am told they cannot prescribe any higher doses. The kratom/7oh doses are consistent
and stable. It may be counterintuitive but the kratom and 7oh are actually way more effective
than opioid medications and they are safer when you look at the research.
Likely what the HB City Council is dealing with is anti-kratom propaganda and lies that have
been floated by people who want kratom eliminated for political and financial reasons. This is
illegitimate and based off of lies. These substances are safe and effective, yet you will
constantly hear, "there is no science to back it up," when actually there are ongoing studies
that show kratom is safe- see the Baylor SAD (single ascending dose) studies and the Johnson
and Johnson studies.
More importantly, no one has ever died from kratom or 7oh -you will hear of isolated cases
but they are NOT confirmed and are mainly cases where kratom may have been in the
person's system at the time of death, but did not cause their death. Again, you will find people
making claims, but there is no science or evidence to back it up.
HB Council: ask yourselves -who is the person/persons that have influenced you to bring
these ban ordinances? Why now and what is tgere evidence? Kratom has been around HB for
over 10 years and yet you're just now hearing about it? The reason is because it's actually
NOT a problem. What's actually going on is that you are being influenced and manipulated
by an external entity who has a political and/or financial interest in seeing it banned. Do not let
this happen!
There is a nationwide effort by certain groups and individuals to try their hardest to get
kratom/7oh banned. Where's the evidence? Where are the dead bodies? Where is the
scientific evidence and proof?
Do NOT fall for this and allow HB residents like me to be made a criminal or to have to do
without and end up bedridden and suffering. I do not deserve to face those circumstances. I
have a really good life and I am a taxpayer and a productive citizen of HB. This is a terrible •
situation, and I call upon each of you to do your diligence and see your way to the truth.
There are many people like me here in HB, California, and the US. We deserve the freedom
to make our own choices and the right to self determination and liberty.
Thank you for hearing me out. Please feel free to ask questions. I will gladly appear and
speak to the Council. I thank you for your time and consideration.
Sincerely,
Henry Northam
From: Sarah Johnson
To: 5uoolementalcommaa surfcity-hb.orq
Subject: Agenda#25-725 and ordinance 4339
Date: Monday,September 15,2025 8:26:34 AM
You don't often get email from sarahandcano@gmail.com.Learn why this is important
To whom it may concern please note that agenda#25-725 and ordinance 4339 I do not
support. Please do not ban kratom and 7-oh. This has given so many families and people that
were dying a new way of life to live. It helps so many people in positive ways. It is also great
for harm reduction. I have close friends and family members who have been able to stop using
fentanyl and are still staying clean and sober now that they have kratom and 7-oh instead. I
personally take 7-oh myself for depression and anxiety and back and nerve pain and freedom
from OxyContin and other controlled substances that are very harmful and deadly. I have a
way of life now that allows me to work and have my own business and raise my children. By
taking away kratom and 7 is stopping our freedom to choose what we want to put in our
bodies. This is now a time where millions of people have to find harm reduction . We have to
stay away from deadly substances . The recovering alcoholic and addict(some of them) doe
not want to be on suboxone and methadone, we want To be able to stay away from old places
and friends and have a helpful substance that can be readily available. Please do not ban
kratom and 7-oh. Please allow us to take care of ourselves in a healthy way.
Thank you for your time
Sarah Johnson
865-242-5156
Mr. Amory Hanson
8102 Ellis Avenue
Apartment 121
Huntington Beach CA 92646
September 16, 2025
The Mayor Of Huntington Beach
2000 Main Street
Huntington Beach CA 92648
My Dear Mister Mayor,
I would like to express my support for Item XIII
Sincerely Yours,
Mr.Amory Hanson
CC:The Honorable Casey McKeon
CC:The Honorable Andrew Gruel
CC:The Honorable Donald C.Kennedy
CC:The Honorable E.M.Twining
CC:The Honorable Grace Vandermark
CC:The Honorable Chad Williams
From: Matthew Weicberoer
To: Suoolementalcomrrasurfcity-hb,orq
Subject: Upcoming hearing on attempt to ban 7-hydroymitragynine.
Date: Monday,September 15,2025 2:22:21 PM
1 You don't often get email from cheflifemw@gmail.com.I earn why this is important
Hi my name is Matthew, I am reaching out today in regards to the upcoming hearing on the
attempt to ban 7 hydroxymitragynine.As myself and many others who have reached out
regarding this ban I am against this idea. I have already previously sent an email with studies
that have been done by the pharmaceutical agency for the United States that has done their due
diligence in testing KRATOM AND 7 HYDROXYMITRAGYNINE. In these tests it shows
evidence of how much kratom and seven hydroxymitragynine can help with so many different
ailments from pain Management to Parkinson's disease to dementia and many others on top of
that. There are so many reasons why this idea of banning kratom is wrong. besides the
scientific reasons it is wrong on a personal level being that I use this safe medicine for my
physical pain. I rather choose to use a medicine that is derived from a plant then use a
pharmaceutical that is extremely addictive and can cause physical harm and death. 7-
hydroymitragynine is the safest and best pain medication I believe to exist currently.
Removing the option to having access to 7-hydroymitragynine would put so many people in
harm's Way and put so many people back in physical and emotional pain and distress. I am a
avid kratom and 7-oh user for my back and knee pain and I need to have this medicine so that
I am able to walk and stand on two feet, so that I'm able to go into work and physically
function so that I can be around others while not being in so much pain to where I can't even
live a normal life to where I can't even be at peace and be happy around others. I am in such
physical pain! the moment that I found kratom it was a blessing from God. I have used
pharmaceutical medications before and yes they help in some ways but in many many other
ways they also caused damage to my liver to my body and put me in horrible withdrawals
when I decided that I wanted to lower my dosage or that I wanted to change medications. It
comparison to kratom the withdrawal symptoms from using kratom or 7 hydroxymitragynine
are nothing compared to any of these other opiates that exist that not only cause these horrible
withdrawals I'm speaking of but also put you at risk of death...the amazing thing about kratom
and 7-hydroymitragynine is that it does not hit the receptors in your brain that affect your
respiratory system when it comes to breathing,this is scientifically been proven this isn't a
debate this isn't a idea or speculation;this is a proven fact and that is one of the biggest
problems that's going on right now with the push to ban kratom and 7-hydroymitragynine no
one is studying it!! In the government(the banning side). It is not being done when it comes to
those who are trying to make the ban. all these false accusations all these false words about
how bad this plant is and how much we need to get rid of it and ban it when there has been no
due diligence done when it comes to hearing from what the people want and to be doing
scientific studies in order to prove your side of wanting to have this beautiful plant and
alkaloid banned. With that I would like to finish off by saying that I wish all those that are in
pain to have access to medication that is safe for the body for the mind and for the consumer at
home.As a human being I have the right to decide what I put into my body as long as it is not
causing physical harm to myself or to others and it is not causing me to be a detriment towards
society. I implore you to please do the right thing and do your due diligence in the proper
manner so that the decision that is made is made scientifically and done with listening to what
us the consumer and people want and do what's right by us the people not by doing what's
right for the pocket and the kratom powder industry that is pushing this entire agenda. Peace
and love to all and thank you for taking the time to read this.
Best regards
Matthew
/Unt,i,: ?/10/02S
rub ,026
H B Wave
PUBLISH DATE: 09/25/2025
CITY OF HUNTINGTON BEACH
LEGAL NOTICE
ORDINANCE NO.4339
Adopted by the City Council on September 16, 2025
"AN ORDINANCE OF THE CITY COUNCIL OF THE CITY OF HUNTINGTON BEACH
AMENDING THE HUNTINGTON BEACH MUNICIPAL CODE BY ADDING NEW CHAPTER
9.92 THEREOF PROHIBITING THE SALE, DISTRIBUTION AND POSSESSION OF KRATOM"
SYNOPSIS:
Ordinance No. 4339 prohibits the sale, distribution, or possession of kratom and other products within the
City of Huntington Beach that contain more than 2% of 7-hydroxymitraginyne in the alkaloid fraction,
recognizing significant health risks associated with elevated concentrations of the alkaloid; prohibits the
sale of any kratom product that is adulterated with synthesized or semi-synthesized-kratom alkaloids or
kratom constituents; and prohibits the sale or distribution of kratom product to a person under 21 years of
age.
Several states and local jurisdictions have prohibited the sale or possession of Kratom, including
Alabama, Arkansas, Indiana, Rhode Island, Vermont, Wisconsin, the City of San Diego (2016), Newport
Beach (2025), and the County of Orange (2025). Kratom is not currently regulated at the federal level, nor
is it prohibited statewide in California.
Penalties for those who violate HBMC §9.92.030 will be guilty of a misdemeanor and may be fined up to
$1000 or be imprisoned in County Jail for not more than six months; and if applicable the Huntington
Beach Business License may be revoked pursuant to HBMC §5.08.300.
COPIES OF THIS ORDINANCE ARE AVAILABLE IN THE CITY CLERK'S OFFICE.
PASSED AND ADOPTED by the City Council of the City of Huntington Beach at a regular meeting held
September 16, 2025 by the following roll call vote:
AYES: Twining, Kennedy, McKeon, Burns, Van Der Mark, Gruel, Williams
NOES: None
ABSENT: None
This ordinance is effective October 16, 2025.
CITY OF HUNTINGTON BEACH
2000 MAIN STREET
HUNTINGTON BEACH, CA 92648
714-536-5227
LISA LANE BARNES, ELECTED CITY CLERK
Column
OFFICIAL AD PROOF
This is the proof of your ad scheduled to run in Huntington Beach Wave on the dates indicated
below. If changes are needed, please contact us prior to deadline at (714) 796-2209.
Notice ID: UXTw0FuJABIAM4r7fQpD I Proof Updated:Sep.18,2025 at 09:59am PDT
Notice Name:Synopsis-Ord No.4339 I Publisher ID:0011756419
See Proof on Next Page
This is not an invoice.Below is an estimated price,and it is
subject to change.You will receive an invoice with the final
price upon invoice creation by the publisher.
FILER FILING FOR
Donna Switzer Huntington Beach Wave
donna.switzer@surfcity-hb.org
(714)374-1649
Columns Wide: 5 Ad Class: Legals
Total Column Inches: 29.12
Number of Lines: 55
09/25/2025:City Notices Notice 442.10
Subtotal $442.10
Tax $0.00
Processing Fee $0.00
Total $442.10
Synopsis - Ord No. 4339 - Page 1 of 2
HB Wave
• PUBLISH DATE:09/25/2025
CITY OF HUNTINGTON BEACH
LEGAL NOTICE
ORDINANCE NO.4339
Adopted by the City Council on September 16,2025
"AN ORDINANCE OF THE CITY COUNCIL OF THE CITY OF HUNTINGTON
BEACH AMENDING THE HUNTINGTON BEACH MUNICIPAL CODE BY ADDING
-NEW CHAPTER 9.92 THEREOF PROHIBITING THE SALE;DISTRIBUTION AND
POSSESSION OF KRATOM"
SYNOPSIS:
Ordinance No. 4339 prohibits the sale, distribution, or possession of kratom and
other products within the City of Huntington Beach that contain more than 20/0 of
7-hydroxymitraglnvne In the alkaloid fraction, recognizing significant health risks
associated with elevated concentrations of the alkaloid;. prohibits.the sale of any
kratom product that is adulterated with synthesized or semi-synthesized kratom
alkaloids or kratom constituents;-and prohibits the sale or distribution of kratom
product to a person under 21'years of age.
Several states and local iurisdlctlons have prohibited the sale or possession of Kratom,
including Alabama,Arkansas, Indiana,Rhode Island,Vermont,Wisconsin,the City of
San Diego (2016),Newport Beach (2025),and the County of Orange'(2025). Kratom Is
not currently regulated at the federal level,nor Is It prohibited statewide In California.
Penalties for those who violate HBMC§9.92.030 will be guilty of a misdemeanor and
may be fined up to 51000 or be imprisoned in County Jail for not more than six months;
and if applicable the Huntington Beach Business License may be revoked pursuant to
HBMC§5.08.300.
COPIES OF THIS ORDINANCE ARE AVAILABLE IN THE CITY CLERK'S OFFICE.
PASSED AND ADOPTED by the City Council of the City of Huntington Beach at a
regular meeting held September 16,2025 by the following roll call vote:
AYES: Twining,Kennedy,-McKeon,Burns,Van Der Mark,Gruel,
Williams
NOES: None
ABSENT: None
This ordinance is effective October 16,.2025.
CITY OF HUNTINGTON BEACH •
2000 MAIN STREET
HUNTINGTON BEACH,CA 92648
714-536-5227
.LISA LANE'BARNES,ELECTED.CITY CLERK
Huntington Beach Wave
Published:9/25/25
•
•
•
•
Synopsis - Ord No. 4339 - Page 2 of 2
INCLUDES THE
FOUNTAIN
VALLEY VIEW
_.. filiii....,,
1920 Main St. Suite 225, Irvine
Irvine, California 92614
(714) 796-2209
legals@inlandnewspapers.com
City of Huntington Beach - City Clerk's Office
2000 Main Street
Huntington Beach, California 92648
Account Number: 5272431
Ad Order Number: 0011756419
Customer's Reference/PO Number:
Publication: Huntington Beach Wave
Publication Dates: 09/25/2025
Total Amount: $442.10
Payment Amount: $0.00
Amount Due: $442.10
Notice ID: UXTw0FuJABIAM4r7fQpD
Invoice Text: HB Wave PUBLISH DATE:09/25/2025 CITY OF HUNTINGTON BEACH LEGAL
NOTICE ORDINANCE NO.4339 Adopted by the City Council on September 16,2025
"AN ORDINANCE OF THE CITY COUNCIL OF THE CITY OF HUNTINGTON
BEACH AMENDING THE HUNTINGTON BEACH MUNICIPAL CODE BY ADDING
NEW CHAPTER 9.92 THEREOF PROHIBITING THE SALE, DISTRIBUTION AND
POSSESSION OF KRATOM"SYNOPSIS: Ordinance No.4339 prohibits the sale,
distribution,or possession of kratom and other products within the City of Huntington
Beach that contain more than 2%of 7-hydroxymitraginyne in the alkaloid fraction,
recognizing significant health risks associated with elevated concentrations of the
alkaloid; prohibits the sale of any kratom product that is adulterated with synthesized
or semi-synthesized kratom alkaloids or kratom constituents;and prohibits the sale or
distribution of kratom product to a person under 21 years of age. Several states and
local jurisdictions have prohibited the sale or possession of Kratom, including
Alabama,Arkansas, Indiana, Rhode Island,Vermont,Wisconsin,the City of San
Diego(2016), Newport Beach(2025),and the County of Orange(2025). Kratom is
not currently regulated at the federal level, nor is it prohibited statewide in California.
Penalties for those who violate HBMC§9.92.030 will be guilty of a misdemeanor and
may be fined up to$1000 or be imprisoned in County Jail for not more than six
months;and if applicable the Huntington Beach Business License may be revoked
pursuant to HBMC§5.08.300. COPIES OF THIS ORDINANCE ARE AVAILABLE IN
THE CITY CLERK'S OFFICE. PASSED AND ADOPTED by the City Council of the
City of Huntington Beach at a regular meeting held September 16, 2025 by the
Synopsis - Ord No. 4339 - Page 1 of 2
See Proof on Next Page
tli INCLUDES THE
FOUNTAIN
VALLEY VIEW
Huntington Beach Wave
1920 Main St.Suite 225,Irvine
Irvine,California 92614
(714)796-2209
2000 Main Street
Huntington Beach, California 92648
AFFIDAVIT OF PUBLICATION
STATE OF CALIFORNIA
County of Orange County
I am a citizen of the United States and a resident of the County
aforesaid; I am over the age of eighteen years, and not a party
to or interested in the above-entitled matter. I am the principal
clerk of the Huntington Beach Wave, a newspaper that has
been adjudged to be a newspaper of general circulation by the
Superior Court of the County of Orange County, State of
California, on July 1, 1998, Case No. A-185906 in and for the
City of Irvine, County of Orange County, State of California;
that the notice, of which the annexed is a true printed copy,
has been published in each regular and entire issue of said
newspaper and not in any supplement thereof on the following
dates,to wit:
0912512025
I certify (or declare) under the penalty of perjury under the
laws of the State of California that the foregoing is true and
correct:
Executed at Anaheim, Orange County,California,on
Date: Sep 25, 2025.
... , Canif,k-
S��ure /
Synopsis - Ord No. 4339 - Page 1 of 2
HB Wave
PUBLISH DATE:09/25/2025
CITY OF HUNTINGTON BEACH
LEGAL NOTICE
ORDINANCE NO.4339
Adopted by the City Council on September 16,2025
"AN ORDINANCE OF THE CITY COUNCIL OF THE CITY OF HUNTINGTON
BEACH AMENDING THE HUNTINGTON BEACH MUNICIPAL CODE BY ADDING
NEW CHAPTER 9.92 THEREOF PROHIBITING THE SALE,DISTRIBUTION AND
POSSESSION OF KRATOM"
SYNOPSIS:
Ordinance No. 4339 prohibits the sale, distribution, or possession of kratom and
other products within the City of Huntington Beach that contain more than 2% of
7-hyciroxymitraginyne in the alkaloid fraction, recognizing significant health risks
associated with elevated concentrations of the alkaloid; prohibits the sale of any
kratom product that is adulterated with synthesized or semi-synthesized kratom
alkaloids or kratom constituents; and prohibits the sale or distribution of kratom
product to a person under 21 years of age.
Several states and local Jurisdictions have prohibited the sale or possession of Kratorn,
including Alabama,Arkansas, Indiana,Rhode Island,Vermont,Wisconsin,the City of
San Diego(2016),Newport Beach (2025),and the County of Orange (2025). Kratom is
not currently regulated at the federal level,nor Is It prohibited statewide in California.
Penalties for those who violate HBMC§9.92.030 will be guilty of a misdemeanor and
may be fined up to$1000 or be imprisoned in County Jail for not more than six months;
and if applicable the Huntington Beach Business License may be revoked pursuant to
H BMC§5.08.300.
COPIES OF THIS ORDINANCE ARE AVAILABLE IN THE CITY CLERK'S OFFICE.
PASSED AND ADOPTED by the City Council of the City of Huntington Beach at❑
regular meeting held September 16,2025 by the following roll call vote:
AYES: Twining,Kennedy,McKeon,Burns,Van Der Mark,Gruel,
Williams
NOES: None
ABSENT: None
This ordinance is effective October 16,2025.
CITY OF HUNTINGTON BEACH
2000 MAIN STREET
HUNTINGTON BEACH,CA 92648
714-536-5227
LISA LANE BARNES,ELECTED CITY CLERK
Huntington Beach Wave -
Published:9/25/25
Synopsis - Ord No. 4339 - Page 2 of 2
�*��ircros. 2
_ 000 Main Street,
a� Huntington Beach,CA
�9=�
__ _� 1,1 City of Huntington Beach 92648
-" APPROVED FOR INTRODUCTIOT
will 7-0
File#: 25-704 MEETING DATE: 9/2/2025
REQUEST FOR CITY COUNCIL ACTION
SUBMITTED TO: Honorable Mayor and City Council Members
SUBMITTED BY: Travis Hopkins, City Manager
VIA: Eric Parra, Chief of Police
PREPARED BY: Shannon Levin, Council Policy Analyst and Kevin Johnson, Captain
Subject:
Approve for Introduction Ordinance No. 4339 Prohibiting the Sale, Distribution and
Possession of Kratom
Statement of Issue:
At the request of Council Woman Gracey Van Der Mark, the Huntington Beach City Council, at its
August 19, 2025, meeting, directed staff to prepare an ordinance prohibiting the sale and distribution
of Kratom within the City. The City Council voted unanimously in support of bringing the ordinance
forward for consideration.
Financial Impact:
Not applicable.
Recommended Action:
Approve for introduction Ordinance No. 4339 "An Ordinance of the City Council of the City of
Huntington Beach Amending the Huntington Beach Municipal Code by Adding New Chapter 9.92
Thereof Prohibiting the Sale, Distribution and Possession of Kratom."
Alternative Action(s):
Do not approve the recommended action and direct staff accordingly.
Analysis:
Kratom is a tropical tree native to Southeast Asia. Its leaves contain psychoactive compounds,
including mitragynine and 7-hydroxymitragynine, which can produce stimulant effects at low doses
and sedative effects at high doses. According to the Drug Enforcement Administration (DEA) and the
National Institutes of Health (NIH), Kratom use has been associated with a range of adverse health
impacts, including psychotic symptoms, dependence, and numerous side effects such as nausea,
vomiting, sweating, constipation, tachycardia, seizures, hallucinations, and hepatotoxicity.
City of Huntington Beach Page 1 of 2 Printed on 8/28/2025
powered by Legistarn"
402
File#: 25-704 MEETING DATE:...9/2/2025. ...
Although Kratom is often marketed for relief of pain, anxiety, opioid withdrawal, and fatigue, there are
no FDA-approved medical uses for the substance. The FDA continues to monitor reports of adverse
events, and current data suggests Kratom's opioid-like properties may expose users to risks of
addiction, abuse, and dependence.
Several states and local jurisdictions have prohibited the sale or possession of Kratom, including
Alabama, Arkansas, Indiana, Rhode Island, Vermont, Wisconsin, the City of San Diego (2016),
Newport Beach (2025), and the County of Orange (2025). Kratom is not currently regulated at the
federal level, nor is it prohibited statewide in California.
The intention of this ordinance is to prohibit the sale, distribution, or possession of kratom and other
products within the City of Huntington Beach that contain more than 2% of 7-hydroxymitraginyne in
the alkaloid fraction, recognizing significant health risks associated with elevated concentrations of
the alkaloid; prohibit the sale of any kratom product that is adulterated with synthesized or semi-
synthesized kratom alkaloids or kratom constituents; and prohibit the sale or distribution of kratom
product to a person under 21 years of age.
Penalties for those who violate HBMC §9.92.030 will be guilty of a misdemeanor and may be fined up
to $1000 or be imprisoned in County Jail for not more than six months; and if applicable the
Huntington Beach Business License may be revoked pursuant to HBMC §5.08.300.
Environmental Status:
This action is not subject to the California Environmental Quality Act (CEQA) pursuant to Sections
15060(c)(2) (the activity will not result in a direct or reasonably foreseeable indirect physical change
in the environment) and 15060(c)(3) (the activity is not a project as defined in Section 15378) of the
CEQA Guidelines, California Code of Regulations, Title 14, Chapter 3, because it has no potential for
resulting in physical change to the environment, directly or indirectly.
Strategic Plan Goal:
Non Applicable -Administrative Item
Attachment(s):
1.Ordinance No. 4339
City of Huntington Beach Page 2 of 2 Printed on 8/28/2025
powered by LegistarTM
403
ORDINANCE NO. 4039
AN ORDINANCE.OF THE CITY COUNCIL OF THE CITY OF HUNTINGTON BEACH
AMENDING THE HUNTINGTON BEACH MUNICIPAL CODE BY ADDING NEW
CHAPTER 9.92 THEREOF PROHIBITING THE SALE,DISTRIBUTION AND POSSESSION
OF KRATOM
The City Council of the City of Huntington Beach does hereby ordain as follows:
SECTION 1. WHEREAS,it is the intent of the City Council to prohibit the sale,
distribution,or possession of kratom and other products within the City of Huntington Beach that
contain more than 2%of 7-hydroxymitragynine in the alkaloid&action,recognizing the
significant health risks associated with elevated concentrations of thisalkaloid;and
Kiatom,(Mitragyna speciosa)IS a tropical tree.native to Southeast Asia,and its leaves are
Often consurried in powdered or extrattform for their stimulant and sedative.effects;and.
The active compounds.in Icratominclucle mitragynine and 74tydroxytnitragynine.While
mitragynine is present in higher concentrations,7-hydroxymitragynine is mote potent and is
largely responsible for the stronger pain-relieving, sedative,and euphoric effects; and
7-hydroxymitragynine binds to opioid receptors in the brain and has:been shown to have
euphoric and mood-enhancing effects,particularly at higher doses,which can increase its appeal
for recreational use;and
7-hydroxytnitragynineis believed to ben ore.potent than morphine in terms of pain
relief. Research has shown that it binds to ppioid receptors in the brain with greater affinity than
morphine,making it significantly more powerful in relieving pain..This greater potency raises
significant concerns about its safety profile,especially regarding the potential for addiction,
overdose,and adverse physical and psychological effects,including nausea,vomiting,and
potential psychosis.These risks are compounded when products contain higher concentrations of
7-hyclroxymitragynine;and
Scientific research and health adviSdrieS have raised concerns Over the safety of baton)
products,particularly those with higher concentrations of 7-hydroxymitragynine,which may
increase the potential for abuse and harm to:public health;and
Several cities in California have taken steps to regulate or baukratom products,
recognizing the need to protect public safety,especially among vulnerable populations.For _
example,Newport Beach,San Diego,.and Oceanside have all enacted a complete ban on the sale,
distribution,and poSsession of all kratom products -irrespective of the concentration of 7-
hydroxymitragynine content;.and
The US.Food and Drug Administration has issued several warning letters to various
compartieS for illegally marketing products containing enhanced levels of 7-
hydroxymitragynine,'culminating in a formal request to the Drug.Enforcement Administration
25-16974/387632
404
ORDINANCE NO, 4339
(DEA)on July 29,2025,to place 7-hydroxymitragynine products on the controlled substance
list;and
The City Council is committed to safeguarding the health and well-being of its residents
•by ensuring that products available for sale do not pose undue health risks;and
The City Council wishes to restrict the-sale and distribution of kratom and other products
containing more than Vo of 7-hydroxymitragynine in the alkaloid ftaction,thereby reducing
potential risks to public health and safety.
SECTION 2.New Chapter 9.92 is added to the Huntington Beach Municipal Code to
read as follows:
"Chapter 992 SALE,DISTRIBUTION,AND POSSESSION OF KRATOM
PROHIBITED
§ 9.92,010 Purpose and Intent.
§9.92.020 Definitions.
§ 9.92,03.0 Sale,distribution and possession of kratorn prohibited.
§ 9.92.040 Violations and Penalties.
§ 9.92.050 Severability.
§ 9.92.010 Purpose and Intent.
This article is enacted pursuant to the City's plenary police powers to protect
public safety,health and welfare,The express purpose of this article is to protect
public health and safety by regulating access to kratorn and other products
containing more.than 2%of 7-hydroxymitragynine in the alkaloid fraction.
§9.92.020 Definitions.
For purposes of this article,the following definitions apply.
(a) "Attractive to children'' means any of the following:
(1)Use of images that are attractive to children,including„but not limited
to,images,of any of the following,,except as part of required health warnings:
(A)Cartoons,tOys,or robots.
(B)Any real or fictional humans.
(C)Fictional animals or creatures.
(D)Fruits or vegetables, except when used to accurately describe
ingredients or flavors,contained in a product..
2
405
ORDINANCE NO:4339
(2)Likeness to iinages, charadterS, or phrases that arepopnlarly used.to
advertise to children.
(3)linitation of candy packaging or labeling,or other packagingand
labeling,Of cereals,'sweets,chips,,or other food products typically marketed to
children.
(4)The terms "'candy" or"candies" or variants in spelling such as"kandy"
or"karidee.
(5)Brand names or close imitations of brand names of eandies,cereals,
sweets,chips,or other food products typically marketed,to.children.
(6)Any Other image or packaging that is eaSily confused*ith
commeicially available foods that do not contain kratom and are typically
marketed to.children
(7)Any other packaging used that is attractive to children considering all
releVant factS..arid Circumstances.
(b) "Kratom,leaf" means the leaf of the kratom plant,also known as mitragyna
speciosa,any.form.
(c) "Kratom leaf tneansthernaterial obtained by extraction of kratoni
leaves by any rleans..
(d) "Kratomproduct" means aproduct consisting of any part of a leaf of the plant
MitragyhaspeCiosa in fresh,dehydrated,or dried form;or a kratom extract,or any
product that contains any kratorii alkaloid or metabolite.
(e)"Total kratom alkaloids" means the sum of mitragyninei speciociliatinc,
speciogynine,paynantheine,and 7-hydroxymitmgynine in a kratom product.
(f)."SyhtheSized" means an alkaloid or alkaloid derivative that has been created
by chemical synthesis or biosynthetic means(including but not limited,to;
fermentation,,recombinant techniques,yeast derived,enzymatic techniques),
rather than traditional food preparation techniques such as heating or extracting.It
also inclUdes alkaloids that has been further exposed to chemicals or prOcesses
that would COnet a structural change in the alkaldids contained within the extract.
§9.92.030 Sale, distribution and possessiorrof kratom prohibited.
(a)Except as otherwise authorized by law;an individual,business,ot other entity
shall not sell,attempt to sell,offer,provide,or distribute a kratom product to a
person under 2,1 years of age..
3
406
ORDINANCE NO: 4339
(b)Except as otherwise atithoriged by law,an individual,,business, or other entity
shall not sell,attetimt,to sell,offer,provide,or distribute any product with a level
of 7-hydroxymitragynine that is greater than 2 percent of the total alkaloids in the
produet,
(c)Except asotherWise authorized by law,,an individual,business;or other entity
shall not sell,attempt to sell,offer,provide,or distribute a kratom product that is
attractive to children..
(d)Any individual,business; Or Other entity that tells;attempts to sel1,offers,
provides, ot distributes a kratom product shall conduct age-verification to ensure
compliance with subdivision(a).
(e)No person or entity shall offerlor sak any kratom product that:contains:or is
adulterated with synthesized or semi-synthesized kratotri alkaloids or kratom
constituents.
§ 9.92.040 Violations and Penalties.
Any person who violates section§ 9.92.030'is guilty of a misdemeanor and upon
conviction thereof may he,punished by a fine,of not more than one thousand
dollar&(Sl.,900.00) or by imprisonment in the County Jail for a.petiod ofnot more
than six.(6)month or by both such fine and imprisonment This section shall not
serve to limit any other legal retteCiieS or aCtiOnS that the City mayhaVe,to
address violations of§9.92.030. A violation of§9.92.030,is:grounds for a
revocation of a business license,if applicable,pursuant to § 50$.300.of the
Huntington Beach Municipal Code.
§ 9.92.050 Severability.
If any section,paragraph, sentence,clause,,phrase or portion of this article is held
invalid or-unconstitutional by any court of competent jurisdiction,such portion
shall be deemed sdverable and such holding shall hot affect the validity of the
remaining portions hereof.The:City CouriCil hereby:declares that it-would have
adopted this article irrespective'of the invalidity of any particular portion thereof
and intends that the invalid portions should be severed,and the balance of the
article'be enforced.
SECTION 3.This'ordinance shall become effective 30 days after its adoption.
4
407
ORDINANCE NO. 4339
PASSED AND ADOPTED by the City Council of the City of Huntington Beach at.a
regular meeting thereof held on ,2025
Mayor
REVIEWED AND APPROVED: ATTEST:
Manager City Clerk
tNI • 'ED ND APP OVED: APPROVED AS TO FORM:
Police Chief City Attorney
5
408
From: Drew Wolfson
To: SupDlementalcommCalsurfcity-hb.org;Andrew.aruel(Tsurfcitv.hb.org;Butch.twinning(asunfcitv.hb.org;
Casev.McKeon(alsurfcitv.hb.org•Chad.willams(alsurfdtv.hb.org;Don.kennedv( surfdtv.hb.org;
Grace.vandermark aClsurfcitv.hb.org;Pat.bums(asurfcity.hb.org
Subject: 70h scheduling
Date: Saturday,August 30,2025 9:23:57 PM
You don't often get email from drewwolfsonl@gmail.com.I earn why this is important
I write to you with sincerity and deep concern. The potential banning of 7-hydroxymitragynine
(7-OH)would not only be a devastating blow to countless people who rely on it, but it could
create a true public crisis. Not one person has died from this. I am a vendor in the public
market im a software engineer worked for some of the top companies in the world. I wanted to
make a difference in the world; so I joined this space. I lost countless friends due to the
pandemic and precipitation drugs, I refuse to lost any more. Follow the science please;
For many, 7-OH has been a godsend—offering relief, stability, and a lifeline where other
options have failed. It has helped people step away from far more dangerous substances,
giving them a chance at a healthier, safer, and more productive life.
If access is taken away, the reality is that overdose rates will rise. Those who have found
safety in 7-OH will be pushed back toward street drugs and high-risk alternatives. Instead of
protecting people, such a ban would expose them to far greater harm.
This is not an abstract policy decision. It is about real lives—about mothers, fathers, sons,
daughters, and friends who have found hope where there once was none. To remove that is to
risk undoing years of progress in harm reduction and public health.
I urge you to consider the human cost. The people who rely on 7-OH are not statistics—they
are our neighbors, family members, and community. This compound has been a bridge away
from danger for so many, and banning it would close that bridge at the exact moment it is
most needed.
With respect and sincerity,
Thank you,
Drew
NEW YORK, NY
DREW WOLFSONI @GMAIL.COM
516-662-8519
From: wakeup777
To: 5uoolementalcomm(@surfcity-hb.org
surfcity-hb.org
Subject: Agenda Item 25-704-Approve for Introduction Ordinance No.4339 Prohibiting the Sale,Distribution and
Possession of Kratom
Date: Saturday,August 30,2025 10:28:25 PM
You don't often get email from wakeup777@protonmail.com. i earn why this is important
Hello,
I'm reaching out in regards to Agenda Item 25-704 - Approve for Introduction Ordinance No.
4339 Prohibiting the Sale, Distribution and Possession of Kratom to be discussed during the
September 2, 2025 Huntington Beach City Council meeting. I wanted to provide some
feedback on what negative affects that the prohibition of selling and possessing of kratom
could have.
Kratom is a plant that has been used for centuries in Southeast Asia. It is related to coffee as
they are both flowering, sub-tropical plants in the Rubiaceae family. This is a plant that has an
alkaloid called mitragynine. Mitragynine has pain relieving properties as it is a partial agonist
of the mu-opioid receptor.
Because kratom is a partial agonist of the mu-opioid receptor, it has been shown to help
people get off of illicit substances such as fentanyl and heroin and there have been countless
testimonies from multitudes of people who have been given their lives back and have once
again been brought back to living lives that are productive to society and productive for their
families after being addicted and homeless from illicit substances. Making the sale and
possession of kratom illegal will rob people in the future from having the potential of being
saved from a life on the streets caused by addiction.
Kratom with its pain relieving effects also helps chronic pain patient who can't afford
healthcare to manage their pain with a wholistic alternative. People who pay for insurance,
sometimes cannot afford the copays, prescription costs or the lack of coverage for testing that
insurance refuses to cover. Some people cannot afford to pay for insurance in the first place,
much less copays, prescription costs and testing costs.
It is a fact that kratom causes far less respiratory depression than even FDA approved
pharmaceuticals and opioids since it is a partial mu-opioid receptor agonist.
Please consider the treatment that this plant can provide for people to get off of illicit
substances and for chronic pain patients to be given relief before making its possession and
sale illegal. Thank you.
From: Dakota Crocker
To: 5uoolementalcommCalsurfcity-hb.orq;Andrew.aruel(Tsurfcitv.hb.orq;Butch.twinninaasurrfcitv.hb.org;
Casev.McKeonPsurfcitv.hb.orq;Chad.willamsaesurfcitv.hb.orq;pon.kennedv(asurfcitv.hb.org;
Grace.vandermark4surfcitv.hb.org;Pat,burns(a surfcitv.hb.orq
Subject: The Benefit of Keeping 7-hydroxymitragynine(7-OH)Legal
Date: Saturday,August 30,2025 11:48:38 PM
You don't often get email from dakotacrock@gmail.com.J earn why this is important
7-hydroxymitragynine (7-OH) is a plant alkaloid that provides a safe and effective
alternative for treating pain and various psychiatric conditions. Unlike alcohol, 7-OH does
not incite violence or idiotic behavior, and an overdose on 7-OH alone cannot cause death.
Additionally, 7-OH is even less toxic than mitragynine, the primary active alkaloid in kratom.
Banning 7-OH while keeping mitragynine legal would be a misinformed decision, as
mitragynine is metabolized into 7-OH in the liver. I believe that keeping 7-OH legal will help
reduce opioid-related deaths, as people will have a safe, non-toxic alternative to potentially
lethal drugs like fentanyl, heroin, and prescription painkillers.
Big kratom companies have sought to make 7-OH a banned substance. They are merely
trying to protect their market share, which has been threatened by 7-OH recently. If public
health were the primary concern, then tobacco and alcohol would be targeted, as they are
much more dangerous substances. An overdose on 7-OH alone has yet to cause a single
death, and it is non-toxic to the body.
Thank you for reading.
From: S E=nand
To: 5uoolementalcomm(asurfcity-hb.orq
Subject: My son died from Kratom powder,not 7oh
Date: Monday,September 1,2025 7:54:02 AM
You don't often get email from switchinz@yahoo.com.I Parn why this is important
My 22 year old son Matthew died from Kratom POWDER (the least potent
form of Kratom available in the United States). He did NOT die from
7oh/7hydroxymitragynine. Kratom caused him to have a seizure, go into
cardiac arrest and die. His toxicology showed he died from the "TOXIC effects
of Mitragynine" an alkaloid found only in kratOm. He had no prescription
drugs, no street drugs nor alcohol in his system when he died, and his autopsy
showed he had no underlying health conditions.
Please email me if you would like his toxicology and autopsy results. Susan
Eppard (Matthew's Mom)
Sent from my iPad
From: laiesiJIP.am
To: suoolementalcommCnlsurfcity-hb.org
Subject: Agenda Item 25-704:Please Delay or Reconsider Kratom Ban
Date: Tuesday,September 2,2025 8:27:56 AM
You don't often get email fromjaredbeam3@gmail.com.Learn why this is important
Dear city council,
I urge you to please delay or reconsider the banning of kratom and its alkaloids (agenda item
25-704). The current push of misinformation against its major alkaloids is driven by lobbying
against a safe alkaloid for market interests, not because of any real danger.
The safety profile of 7-OH is demonstrated by over 500 million doses of 7-OH and no
confirmed deaths from it alone. Studies also show it's a partial-agonist that doesn't bind to the
receptors that cause respiratory depression. Kratom, which likewise does not affect those
receptors, has been safely used by millions for much longer.
Removing access to these safe harm reduction tools will put people at risk. There is no
emerging public health threat from kratom or its alkaloids that justifies a ban.
Thank you for your time. I pray you'll keep the public's safety in mind and protect safe harm
reduction options.
Best,
Jared beam
From: Matthew Weicberger
To: suoolementalcommftsurfcity-hb.orq
Subject: Matthew An advocate for kratom and 7oh
Date: Tuesday,September 2,2025 8:28:20 AM
Attachments: jcon.onq
jcon.pnq
IYou don't often get email from cheflifemw@gmail.com.J earn why this is important
Hello my name is Matthew. I am reaching out to you in regards to the upcoming hearing that
you have regarding the action to ban kratom in Huntington Beach California. I oppose to this
idea. The thought that our political leaders want to take away and alkaloid/medicine that
provides relief as well as harm reduction and so many benefits that range from pain relief to
emotional relief to anxiety relief and others; In my opinion the idea of banning kratom is
nonsensical and will only bring harm to many who are trying to live a decent life. I'm
attaching below a document and a written article that is written by the national library of
medicine. I welcome you to please read through this information I would like to bet that after
doing so there would be a change of heart and this would not come from sympathy or
compassion but from scientific proof from studies and due diligence being done on this
beautiful plant and alkaloid that millions of us on this planet use so that we can live a normal
decent life. Thank you kindly for your time and I hope that the right decision is made;that the
decision for the people is made; one that is for the people and not for the money.
Kind regards
Matthew.
Hello my name is Matthew.I am reaching out to you in regards to the upcoming hearing that you have regarding the
action to ban kratom in Huntington Beach California.I oppose to this idea.The thought that our political leaders want to
take away and alkaloid/medicine that provides relief as well as harm reduction and so many benefits that range from
pain relief to emotional relief to anxiety relief and others;In my opinion the idea of banning kratom is nonsensical and
will only bring harm to many who are trying to live a decent life.I'm attaching below a document and a written article
that is written by the national library of medicine.I welcome you to please read through this information I would like to
bet that after doing so there would be a change of heart and this would not come from sympathy or compassion but from
scientific proof from studies and due diligence being done on this beautiful plant and alkaloid that millions of us on this
planet use so that we can live a normal decent life.Thank you kindly for your time and I hope that the right decision is
made;that the decision for the people is made;one that is for the people and not for the money.
Kind regards
Matthew.
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Pharmaceuticals (Basel). 2025 Feb 6;18(2):222.
doi: 10.3390/ph18020222
Exploring the Therapeutic
Potential of Mitragynine and
Corynoxeine: Kratom-Derived
Indole and Oxindole Alkaloids
for Pain Management
Ahmed S Alford 1,*, Hope L Moreno 1, Menny M
Benjamin 1, Cody F Dickinson 1, Mark T
Hamann 1
Editor: Rejean Couture
Author information Article notes
Copyright and License information
PMCID: PMC11858930 PMID: 40006036
Abstract
The search for effective pain management
solutions remains a critical challenge, especially
amidst growing concerns over the use of
conventional opioids. In the US, opioid-related
mortality rates have surged to as many as 80
deaths per 100,000 people in some states, with
an estimated economic burden of USD 1.5
trillion annually—exceeding the gross domestic
product (GDP) of most US industrial sectors. A
remarkable breakthrough lies in the discovery
that indole and oxindole alkaloids, produced by
several genera within the plant Tribe Naucleeae,
act on opioid receptors without activating the
beta-arrestin-2 pathway, the primary driver of
respiratory depression and overdose deaths.
This systematic review explores the
pharmacological properties, mechanisms of
action, dosing considerations, interactions, and
long-term effects of mitragynine and
corynoxeine, alkaloids from the Southeast Asian
plant Mitragyna speciosa (kratom) and others in
the Tribe Naucleeae. Mitragynine, a partial
opioid receptor agonist, and corynoxeine, known
for its anti-inflammatory and neuroprotective
effects, demonstrate significant therapeutic
potential for managing diverse pain types—
including neuropathic, inflammatory,
nociceptive, visceral, and central pain
syndromes—with a focus on cancer pain. Unlike . .
traditional opioids, these compounds do not .
recruit beta-arrestin-2,-avoiding key adverse
effects such as respiratory depression, severe
constipation, and rapid tolerance development.
Their distinct pharmacological profiles make . .
them innovative candidates for safer, non-lethal
pain relief. However, challenges persist,
including the unregulated nature of kratom
products, inconsistencies in potency due to
crude extract variability, potential for misuse,
and adverse drug interactions. Addressing these
issues requires establishing standardized quality
control protocols, such as Good Manufacturing
Practices (GMP), to ensure consistent potency
and purity. Clear labeling requirements with
dosage guidelines and warnings should be
mandated to ensure safe use and prevent
misuse. Furthermore, the implementation of
regulatory oversight to monitor product quality
and enforce compliance is essential. This review
emphasizes the urgency of focused research to
optimize dosing regimens, characterize the
pharmacodynamic profiles of these alkaloids,
and evaluate long-term safety. By addressing
these gaps, the mitragynine- and corynoxeine-
related drug classes can transition from
promising plant-derived molecules to validated
pharmacotherapeutic agents, potentially
revolutionizing the field of pain management.
Keywords: mitragynine, corynoxeine, pain
management, Mitragyna speciosa, systematic
review, pharmacology, 13-arrestin, opioids
1. Introduction
The search for effective pain management
solutions remains a critical challenge, especially
amidst growing concerns over the side effects
and dependency risks associated with
conventional opioids. In the United States,
opioid misuse has led to significant mortality and
economic burden, with opioid-related deaths
estimated at 80 per 100,000 individuals in some
states and an annual cost of approximately USD
1.5 trillion [1]. Amid this crisis, certain indole and
oxindole alkaloids from the plant tribe
Naucleeae have emerged as promising
alternatives due to their ability to engage opioid
receptors without activating the I3-arrestin-2
pathway, a key mediator of respiratory
depression and other severe opioid side effects
[2].
The alkaloid composition of Mitragyna
speciosa (kratom) is dominated by mitragynine,
which constitutes approximately 66.2% of the
total alkaloid content in commercial kratom
products. In contrast, 7-hydroxymitragynine,
despite its higher potency at opioid receptors, is
a minor component, accounting for only 0.01-
0.03% of the total alkaloids. Other significant
alkaloids include speciociliatine (8.6-16.6%),
paynantheine (9.0-16.0%), and speciogynine
(6.6-8.6%), with trace amounts of additional
alkaloids such as corynoxeine, isocorynoxeine,
and speciophylline. These secondary alkaloids
may also contribute to kratom's pharmacological
profile but in a less pronounced manner. The
variability in alkaloid composition across kratom
products is influenced by factors such as
genetic differences, environmental conditions,
and processing methods, resulting in
inconsistencies that affect their pharmacological
effects and safety profiles.
Among these compounds, mitragynine and
corynoxeine, derived from the Southeast Asian
plant Mitragyna speciosa (Figure 1), commonly
known as kratom, stand out as potentially safer
alternatives to traditional opioids. While kratom
contains a range of bioactive alkaloids, the
oxindoles, including corynoxeine and its
stereoisomer isocorynoxeine, are minor yet
significant tetracyclic oxindole alkaloids. Kratom
also contains other active compounds, such as
flavonoids, polyphenols, and terpenoids, which
contribute to the pharmacological effects of the
raw plant products and crude plant extract.
These oxindoles also occur in higher
concentrations in other plants, such as species
within the Uncaria genus, further highlighting
their pharmacological importance [3].
Mitragynine, an indole alkaloid, is recognized as
a partial agonist of the mu-opioid receptor
(MOR), whereas corynoxeine demonstrates
notable anti-inflammatory and neuroprotective
properties. Unlike conventional opioids, both
mitragynine and corynoxeine lack 13-arrestin
recruitment, which reduces risks of adverse
effects such as respiratory depression,
constipation, and tolerance development [4].
This unique pharmacological profile positions
them as promising candidates for managing
various types of pain—including neuropathic,
inflammatory, nociceptive, visceral, and central
pain syndromes—with a particular focus on
cancer-related pain.
Figure 1.
Figure 1
Open in a new tab
Mitragyna speciosa, commonly known as
kratom, contains bioactive secondary
metabolites, specifically indoles (e.g.,
mitragynine) and oxindoles (e.g., corynoxeine).
This review focuses specifically on mitragynine
and corynoxeine as representative compounds
of the indole and oxindole alkaloid classes,
respectively. Although kratom is traditionally
consumed in its whole form (e.g., crude leaves
or powdered leaves), isolating and examining
these two compounds allows for a targeted
analysis of their unique therapeutic potential,
mechanisms of action, and safety profiles. By
focusing on mitragynine and corynoxeine, this
review seeks to reflect the broader
pharmacological potential of indole and oxindole
alkaloids, addressing their potential applications
in pain management without the confounding
factors present in whole-plant kratom
formulations. For reference, Table 1 and Table
2 present the principal structures of the oxindole
and indole alkaloids derived from Mitragyna
speciosa, providing an overview of these
compounds' structural diversity relevant to their
pharmacological profiles.
Table 1.
Principal structures of oxindole alkaloids
of Mitragyna speciosa.
la
Compound R1 3 7 15 20 R2
Corynoxeine H S R S R CHCH2
Corynoxine A H S S S S CH2CH3
Corynoxine B H S R S S CH2CH3
Mitrafoline OH S S S S CH2CH3
Speciofoline OH R R S S CH2CH3
Specionoxeine OCH3 S R S R CHCH2
Rhynchophylline H S R S R CH2CH3
Rotundifoline OH S S S R CH2CH3
Rotundifoleine OH S S S R CHCH2
Open in a new tab
Table 2.
Principal structures of indole alkaloids
of Mitragyna speciosa.
B;
Compound R1 3 15 20 R2
Mitragynine OCH3 S S S CH2CH3
Speciogynine OCH3 S S R CH2CH3
Speciociliatine OCH3 R S S CH2CH3
Mitraciliatine OCH3 R S R CH2CH3
Paynantheine OCH3 S S R CHCH2
Corynantheidine OH S S S CH2CH3
Open in a new tab
Despite these promising pharmacological
profiles, challenges remain, particularly around
the unregulated nature of kratom products,
variability in dosage, and potential for abuse.
This review aims to identify and critically assess
relevant studies to provide an in-depth
understanding of the current evidence
surrounding mitragynine, corynoxeine, and other
kratom-derived alkaloids. While no clinical trials
have yet defined therapeutic doses or
established guidelines, the preclinical and
observational data reviewed here may offer
preliminary insights that could inform future
research. This synthesis is intended to support
clinicians and researchers in gaining a
foundational understanding of these
compounds' potential pharmacological profiles
and mechanisms, and to encourage further
investigation into their role in pain management
and other therapeutic areas. Policymakers and
the general public may also find this review
beneficial in understanding the complex
landscape of kratom's benefits and risks as they
relate to public health considerations.
2. Results
2.1. Pharmacodynamics
Corynoxeine's mechanisms of action suggest
significant potential in the treatment of pain
through several pathways:
Anti-Inflammatory Agent: Corynoxeine's role as
an anti-inflammatory agent is critical in
managing pain linked to inflammation, a
common cause in conditions such as arthritis
and autoimmune diseases. Through inhibition of
vascular smooth muscle cell (VSMC)
proliferation, particularly by blocking the
extracellular signal-regulated kinase (ERK1/2)
phosphorylation pathway, corynoxeine reduces
inflammatory processes in vascular and tissue
contexts. This anti-inflammatory activity can
help mitigate pain by lessening the release of
pro-inflammatory cytokines and mediators that
typically heighten pain sensitivity. By targeting
inflammation pathways, corynoxeine supports
tissue health and reduces the potential for
chronic pain development [5,6].
Neuroprotective Actions and Autophagy
Enhancement: Corynoxeine serves as a
neuroprotective agent, offering significant
potential in conditions associated with
neuropathic pain where nerve cell damage or
dysfunction contributes to pain perception.
Through the enhancement of autophagy,
corynoxeine helps clear neurotoxic protein
aggregates such as alpha-synuclein, which can
otherwise accumulate and cause neural stress
and degeneration. By engaging pathways like
Akt/mTOR to induce autophagy, corynoxeine
may reduce neuronal death and maintain nerve
function, effectively lowering pain signals
associated with damaged or impaired nerves.
This neuroprotective mechanism could be
beneficial in conditions like peripheral
neuropathy and neurodegenerative diseases,
where nerve protection aligns with pain
mitigation [6,7].
Calcium Channel Blockade and Vasorelaxation:
Corynoxeine induces vasorelaxation by blocking
L-type calcium channels in vascular smooth
muscle cells, thus preventing the influx of
calcium ions. Calcium ions play a critical role in
smooth muscle contraction; by limiting their
entry, corynoxeine reduces smooth muscle tone
and relaxes blood vessels. This vasodilation
effect is particularly beneficial in conditions
where vascular constriction is linked to pain,
such as migraines and certain vascular pain
syndromes. Enhanced blood flow from reduced
vascular resistance can alleviate symptoms by
improving oxygenation and nutrient delivery to
affected tissues, thus reducing ischemic or
tension-induced pain [6,7,$].
Adrenergic Receptor Antagonism: By inhibiting
a1A adrenergic receptors, corynoxeine further
promotes vasodilation, countering the effects of
adrenergic-mediated vasoconstriction.
Adrenergic receptors, when activated, increase
vascular tone, which can exacerbate pain in
conditions like tension headaches and
hypertension-related discomfort. Corynoxeine's
antagonism of these receptors allows for
relaxation of blood vessels, which can ease pain
by reducing the stress and pressure within the
vascular system. This mechanism adds a layer
of vascular relief in pain conditions where
adrenergic activity contributes to vascular
tightness and discomfort [9,10].
Potassium Channel Activation and Vascular
Smooth Muscle Relaxation: As a potential
potassium channel opener, corynoxeine
hyperpolarizes vascular smooth muscle cells,
further reducing cellular excitability and
promoting vasodilation. The activation of
potassium channels encourages the efflux of
potassium ions, stabilizing the cellular
membrane potential away from depolarization
thresholds that trigger contraction. This action
complements calcium channel inhibition,
creating a dual mechanism for smooth muscle
relaxation. By decreasing vascular resistance
and enhancing blood flow, corynoxeine's
potassium channel activation may help alleviate
pain from vascular sources, as seen in migraine
and other vascular pain disorders [6,7].
Prevention of Vascular Smooth Muscle Cell
Proliferation: Corynoxeine also inhibits the
proliferation of vascular smooth muscle cells
(VSMCs), an effect particularly relevant in
conditions like atherosclerosis and restenosis,
where abnormal cell growth contributes to
vascular narrowing and pain. By blocking the
ERK1/2 pathway, corynoxeine disrupts the
signaling required for VSMC proliferation, which
can prevent or slow down the progression of
vascular blockages. This mechanism is
essential in managing chronic pain linked to
vascular diseases, as maintaining healthy,
unobstructed vessels can reduce ischemic pain
and improve blood circulation to affected
regions [7,a].
In summary, corynoxeine's multi-faceted
mechanisms—including its roles as an anti-
inflammatory agent, neuroprotective agent,
calcium channel blocker, adrenergic receptor
antagonist, and potassium channel opener—
highlight its potential in effectively managing and
treating various types of pain.
Mitragynine's mechanisms of actions also
suggest significant potential in the treatment of
pain but through unique polypharmacology
pathways (summarized in Figure 2).
Figure 2.
Figure 2
Open in a new tab
Polypharmacology of mitragynine, the principal
indole alkaloid derived from Mitragyna speciosa.
Mu-Opioid Receptor (MOR) Partial Agonist:
Mitragynine acts as a partial agonist at mu-
opioid receptors (MOR), which are primary
targets for traditional opioid analgesics. With a
binding affinity of approximately 0.233 pM,
mitragynine can activate MOR to produce
analgesic effects but with limited efficacy
compared to full agonists like morphine. This
partial agonism allows mitragynine to provide
pain relief while significantly reducing the side
effects typically associated with opioid receptor
activation, including respiratory depression and
high potential for addiction. The decreased
ability to fully activate MOR is linked to a
reduced risk of tolerance development, meaning
that patients are less likely to need increasing
doses over time to achieve the same level of
pain relief. Additionally, the partial agonism at
MOR may result in lower risks of gastrointestinal
side effects, such as constipation, which is a
common issue with traditional opioids [9.,14,11].
Kappa-Opioid Receptor (KOR) Antagonist: In
contrast to its partial agonism at MOR,
mitragynine functions as an antagonist at
kappa-opioid receptors (KOR). KOR activation
is often associated with dysphoria,
hallucinations, and a reduction in reward-
seeking behaviors. By antagonizing KOR,
mitragynine reduces these adverse effects,
potentially providing mood-stabilizing effects
and lessening dysphoric reactions. KOR
antagonism also contributes to pain relief, as
KOR can play a role in modulating pain
perception, especially in conditions where stress
and mood are exacerbated by pain. This dual
MOR agonism and KOR antagonism may offer
a balanced analgesic effect while avoiding some
of the psychological side effects of KOR
agonists [12].
Competitive Antagonist at Serotonin Receptors
(5-HT2A): Mitragynine acts as a competitive
antagonist at the 5-HT2A serotonin receptor,
which modulates the release of various
neurotransmitters involved in mood, cognition,
and pain perception. By blocking 5-HT2A
receptors, mitragynine can reduce serotonin-
related neurotransmission, which may help in
stabilizing mood and controlling pain perception,
particularly in individuals with anxiety or
depression-related pain. This antagonism is also
thought to reduce anxiety and prevent
overstimulation of neural pathways, contributing
to an improved quality of life for those with
chronic pain [2,1.0].
Partial Agonist at 5-HT1A: As a partial agonist at
the 5-HT1A receptor, mitragynine can enhance
serotonin signaling to some extent, particularly
in ways that are anxiolytic and mood-enhancing.
The 5-HT1A receptor is linked to improved
mood and anxiety reduction, both of which are
beneficial in chronic pain management, as pain
can be exacerbated by psychological stress and
anxiety. By partially activating this receptor,
mitragynine may improve the psychological
state of individuals suffering from chronic pain,
which indirectly aids in pain management by
reducing pain perception linked to stress and
anxiety [9,1Q].
Binding to 5-HT2B and 5-HT2C Receptors:
Mitragynine has weaker interactions with 5-
HT2B and 5-HT2C serotonin receptors, binding
with a Ki of approximately 1260 nM. While these
interactions are less pronounced than its actions
on other receptors, they may have subtle
modulatory effects on mood and cognition.
Since 5-HT2B and 5-HT2C receptors are
involved in the regulation of mood and appetite,
the slight binding affinity could contribute to
mitigating symptoms like irritability or loss of
appetite in individuals with chronic pain,
although the impact is likely minor compared to
its effects on other receptors [9,1Q].
Alpha-2 Adrenergic Receptor Agonist: Acting as
an agonist at alpha-2 adrenergic receptors,
mitragynine engages mechanisms similar to
clonidine, a drug used to manage opioid
withdrawal symptoms. Alpha-2 agonism can
reduce norepinephrine release, which calms the
sympathetic nervous system and provides a
sense of relaxation and reduced arousal. This
agonism is particularly useful for managing
symptoms of opioid withdrawal, including
cravings, irritability, and heightened pain
sensitivity. The activity at alpha-2 receptors may
also contribute to the overall analgesic effect of
mitragynine by reducing sympathetic responses
that can intensify pain perception in stressful
situations [2.,1 ].
Dopamine D2 Receptor Affinity: Mitragynine's
affinity for dopamine D2 receptors suggests
potential antipsychotic effects, which may
alleviate symptoms of psychosis in vulnerable
individuals. By interacting with D2 receptors,
mitragynine could theoretically reduce excessive
dopamine activity, which is linked to conditions
such as schizophrenia and bipolar disorder. For
chronic pain patients, this dopaminergic
modulation might help in managing pain
perception and emotional responses, as well as
in mitigating the negative psychological
symptoms sometimes associated with chronic
pain, such as anhedonia and low motivation
[14].
[3-Arrestin Activity: Unlike traditional opioids,
mitragynine does not recruit R-arrestin 2 at the
mu-opioid receptor, which is significant because
R-arrestin 2 recruitment is linked to several
adverse effects of opioids, including respiratory
depression, constipation, and tolerance [15].
The absence of R-arrestin 2 recruitment in
mitragynine's mechanism suggests a potentially
safer side effect profile, offering effective pain
relief without the heightened risks associated
with conventional opioids. This property is a
crucial factor in its unique pharmacological
safety, making it a promising candidate for
further research in pain management settings.
Cannabinoid Receptor Modulation: Mitragynine
also interacts with cannabinoid receptors,
particularly CBI and CB2, which play roles in
modulating pain and inflammation. Research
indicates that mitragynine's analgesic effects,
particularly in neuropathic pain, may be
mediated through these cannabinoid pathways.
For instance, in models of chemotherapy-
induced peripheral neuropathy, the analgesic
effect of mitragynine was lessened when
cannabinoid receptors were blocked, suggesting
that these receptors are instrumental in its effect
on neuropathic pain. This cannabinoid receptor
interaction provides a unique avenue for pain
relief, especially in complex pain conditions
involving both central and peripheral
mechanisms [16].
TRPV1 Modulation: Recent studies have shown
that mitragynine may modulate the Transient
Receptor Potential Vanilloid 1 receptor (1), a
non-opioid pathway involved in sensing noxious
stimuli, such as heat and inflammation. By
affecting TRPV1 receptors, mitragynine can
potentially reduce pain signaling in inflammatory
and neuropathic pain conditions. TRPV1
modulation is particularly relevant for pain states
where peripheral sensitization occurs, as
blocking or modulating these receptors
decreases the activation of pain pathways. This
pathway represents an additional analgesic
mechanism that can complement its opioid-like
effects [17].
The absence of significant Delta-Opioid
Receptor (DOR) activity in both mitragynine and
corynoxeine indicates that their analgesic and
neuroprotective effects are mediated through
other pathways [12.]. DORs are involved in
modulating pain, mood, and neuroprotection,
but DOR agonists are associated with the risk of
convulsions and other adverse effects.
2.2. Pharmacokinetics
Mitragynine, the principal indole alkaloid in
Mitragyna speciosa (kratom), exhibits distinctive
pharmacokinetic properties that are crucial to its
therapeutic applications. It is a lipophilic weak
base (pKa -8.1) with high plasma protein
binding (85-95%) and undergoes extensive
hepatic metabolism through both phase I
(oxidation, demethylation) and phase II
(glucuronidation, sulfation) pathways.
The pharmacokinetics of mitragynine
demonstrate dose-dependent variations, with
key parameters providing insights into its
behavior. After a single dose, the Cmax ranged
from 17.1 ng/mL (6.65 mg dose) to 125 ng/mL
(53.2 mg dose), while at steady-state
(Cmax,ss), it ranged from 21.4 ng/mL to 143
ng/mL. The Tmax remained consistent across
both single and multiple doses, ranging from 1.0
to 1.7 h. The elimination half-life (t1/2) increased
significantly with dose, ranging from 8.5 h at the
lowest dose to 43.4 h at the highest dose for
single dosing, and from 25.7 to 67.9 h at steady
state. Systemic exposure, measured as
AUCO—co, increased proportionally with dose,
ranging from 52.8 h•ng/mL to 908 h•ng/mL after
a single dose, while steady-state AUC
(AUCO—T,ss) ranged from 85.1 h•ng/mL to 958
h•ng/mL. Clearance (CL) decreased with
increasing doses, ranging from 278 L/h at lower
doses to 94 L/h at higher doses, indicating
nonlinear pharmacokinetics. The volume of
distribution (Vd) also increased with dose, from
1349 L to 3788 L for single doses and from
2980 L to 6020 L at steady-state, reflecting
extensive tissue distribution [18]. These findings
highlight the importance of dose adjustments to
account for significant changes in clearance and
half-life at higher doses.
A significant factor influencing the
pharmacokinetics of mitragynine is the variability
between administering pure mitragynine versus
raw kratom products. Raw kratom contains a
complex mixture of alkaloids and bioactive
compounds that can alter absorption,
metabolism, and clearance, resulting in greater
variability in pharmacokinetic parameters. For
instance, other alkaloids in raw kratom may
competitively inhibit or enhance mitragynine
metabolism, affecting Cmax, Tmax, and t1/2.
Furthermore, no standardization of kratom
formulations or dosing exists, making it
challenging to establish predictable therapeutic
outcomes or mitigate potential adverse effects.
The pharmacokinetics of corynoxeine exhibit
notable differences between normal
physiological conditions and CUMS-induced
depression models, which are essential to
consider for therapeutic applications. In normal
rats, the maximum plasma concentration
(Cmax) of corynoxeine was 407.48 ± 10.87
ng/mL, with a time to reach Cmax (Tmax) of
1.67 ± 0.24 h. In contrast, CUMS-induced
depression rats demonstrated a lower Cmax of
306.83 ± 18.72 ng/mL and a delayed Tmax of
2.33 ± 0.47 h, indicating reduced absorption
under pathological conditions. The elimination
half-life (t1/2) was slightly longer in CUMS-
induced depression rats (2.68 ± 0.30 h)
compared to normal rats (2.40 ± 0.12 h), while
the clearance rate (CL) was faster in the
depression model (18.06 ± 1.36 L/h/kg versus
14.48 ± 0.61 L/h/kg in normal rats), suggesting a
reduced systemic exposure to the compound
[14].
Additionally, the volume of distribution (Vd) was
significantly higher in CUMS-induced
depression rats (69.15 ± 3.25 L/kg) compared to
normal rats (50.09 ± 2.11 L/kg), implying greater
tissue penetration in the pathological state. The
area under the concentration—time curve (AUC),
representing overall drug exposure, was
reduced in CUMS-induced rats, with AUCO-t
values of 1202.97 ± 39.79 ng•h/mL versus
1495.62 ± 55.23 ng•h/mL in normal rats and
AUCO-°° values of 1614.48 ± 119.62 ng•h/mL
versus 1914.65 ± 95.66 ng•h/mL, respectively
[14]. These findings highlight a significant
impact of depression on corynoxeine's
pharmacokinetics, including reduced absorption,
faster clearance, and greater distribution into
tissues.
The altered pharmacokinetic parameters in the
depression model underscore the influence of
pathological conditions on the behavior of
corynoxeine within the body. These differences
emphasize the need for tailored dosing
regimens in clinical applications to ensure
therapeutic efficacy and safety in patients with
underlying conditions. Understanding these
variations provides a foundation for optimizing
the use of these compounds in different
physiological and pathological contexts.
Furthermore, these disparities underscore the
necessity of further research to optimize
standardization; characterize dose—response
relationships, and establish regulatory
frameworks for the safe and effective clinical
use of mitragynine and kratom products.
3. Discussion
3.1. Summary of Findings
Mitragynine and corynoxeine exhibit significant
potential in effectively managing and treating
various types of pain through their multifaceted
mechanisms of action. When addressing pain
management, there is a large basis of
pharmacotherapy because of the vastly diverse
pathophysiology: While these compounds hold.
significant potential in neuropathic pain.
(chemotherapy-induced peripheral neuropathy
(CIPN), diabetic neuropathy, postherpetic
neuralgia), inflammatory pain, nociceptive pain
(post-surgical, musculoskeletal), visceral pain
(IBS, endometriosis), and central pain
syndromes (MS, spinal cord injury), cancer pain
is the most notable for effective.management.
Cancer pain presents a unique challenge in pain
management due to its complex and
multifaceted nature, often involving a
combination of nociceptive; neuropathic, and
inflammatory components. Traditional opioids
like morphine have long been the mainstay for
cancer pain management; however, their use is
associated with significant drawbacks, including
the risk of tolerance, dependence, respiratory
depression, and constipation. Furthermore,
recent studies have suggested that morphine
and other opioids may promote tumor growth
and metastasis by enhancing angiogenesis and
suppressing immune function [19,20]. This
potentially adverse effect on cancer progression
highlights the need for alternative analgesics
that do not compromise cancer treatment
outcomes.
Mitragynine and corynoxeine offer promising
alternatives to traditional opioids for cancer pain
management. Mitragynine, a partial agonist at
mu-opioid receptors, provides effective
analgesia while reducing the risk of severe side
effects associated with full opioid agonists [ i].
Its lack of beta-arrestin 2 recruitment minimizes
the risks of respiratory depression, constipation,
and tolerance development. Additionally,
mitragynine's partial agonist activity at 5-HT1A
receptors and antagonist activity at 5-HT2A
receptors may offer mood-enhancing and
anxiolytic benefits, which are crucial for the
overall well-being of cancer patients [10,21].
Corynoxeine, with its potent anti-inflammatory
and neuroprotective properties, can further
enhance pain relief in cancer patients. Its ability
to reduce inflammation and protect neurons
from damage is particularly beneficial in
managing pain caused by tumor growth and
metastasis [$,22]. Corynoxeine's vasorelaxant
effects, mediated through calcium channel
blocking and adrenergic receptor antagonism,
can help alleviate pain associated with tumor-
induced vascular tension and improve blood
flow to affected tissues [[,22].
Moreover, neither mitragynine nor corynoxeine
has been shown to promote tumor growth,
making them safer options for cancer patients
compared to traditional opioids [2,1,24]. By
offering effective analgesia without the risk of
enhancing tumor progression, these compounds
represent a significant advancement in the
management of cancer pain. The combined
pharmacological actions of mitragynine and
corynoxeine, including their opioid receptor
modulation, anti-inflammatory effects, and
neuroprotective properties, position them as
superior alternatives to traditional opioids like
morphine for cancer pain management. Their
potential to provide comprehensive pain relief
while minimizing adverse effects and supporting
overall patient health underscores their
importance in the evolving landscape of cancer
pain therapeutics.
3.2. p-Arrestin Activity
G-protein-coupled receptors such as the opioid
receptors are transmembrane receptors that are
capable of recruiting proteins [i-arrestins to
initiate separate cellular signal transduction
pathways [12]. One of the most promising
aspects of the major alkaloids found
in Mitragyna speciosa is their lack of beta-
arrestin 2 recruitment. Traditional opioids like
morphine and fentanyl not only activate G-
protein signaling pathways to provide pain relief
but also recruit beta-arrestin 2. This recruitment
is associated with many adverse effects, such
as respiratory depression, constipation, and the
development of tolerance and dependence.
Beta-arrestin 2 mediates these effects by
desensitizing the receptors, internalizing them,
and initiating altern
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From: Matthew Weicberger <cheflifemw@gmail.com>
Sent: Saturday,August 30, 2025 1:54 AM
To: supplementalcomm@surfcity-hb.org
Subject: Matthew An advocate for kratom and 7oh
' Y
You don't often get email from cheflifemw@gmail.comn Learn why this is important
Hello my name is Matthew. I am reaching out to you in regards to the upcoming hearing that you have
regarding the action to ban kratom in Huntington Beach California. I oppose to this idea.The thought that
our political leaders want to take away and alkaloid/medicine that provides relief as well as harm
reduction and so many benefits that range from pain relief to emotional relief to anxiety relief and others;
In my opinion the idea of banning kratom is nonsensical and will only bring harm to many who are trying
to live a decent life. I'm attaching below a document and a written article that is written by the national
library of medicine. I welcome you to please read through this information I would like to bet that after
doing so there would be a change of heart and this would not come from sympathy or compassion but
from scientific proof from studies and due diligence being done on this beautiful plant and alkaloid that
millions of us on this planet use so that we can live a normal decent life.Thank you kindly for your time
and I hope that the right decision is made;that the decision for the people is made; one that is for the
people and not for the money.
Kind regards
Matthew.
Hello my nameis Matthew.I am reaching out to you in regards to th.eupcoming hearing that you have regarding the action:to ban.
kratom in,Huntington Beach California.I oppose to this idea The th :w oughtthat our political leadersant to take away and alkaloid%
medicine that provides relief as well as harm reduction and so many benefits that range from pain relief:to emotional relief to anxiety_
relief and others;In,my opinion the idea of banning kratom is nonsensical and will only bring harm to many who are trying to live a :. .
decent life.I'm attaching below doc:ument_and a written article th.at,is written by the national library of medicine.I welcome you to
please read through this information I would like to bet that after doing:se there would be a change of heart and this.would not come.,
from sympathy or compassion but from scientific proof from studies and due diligence being done on this beautiful plant and
alkaloid that millions of us on this planet use so that we can live a normal decent life..Thankyou kindly for ryour.time and Ihope that
the right decision is made;that the decision for the people is made;one that is for the people and not for the money.
Kind re ards
Matthew:.:
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Pharmaceuticals (Basel)
_
. 2025 Feb 6;18(4222i doi: 10.3390/ph18020222
p g �the Th
erapeutic eutic Potential
Exl orin p of Mitragynine and
CorY noxeine:" Kratom=Derived Indole and Oxindole Alkaloids for
Pain Management
:Ahmed S`Atford HopeLMoreno 1, Mennv M Benia min Codv
F. Dickinson:' Mark T Hamann '"
Editor: Rejean Couture' •
• Author information
• Article notes. •
•• Copyright and License information ,
.
PM CI D`..PM C11858930.-PM I D: 40006036
Abstract
The•search foreffective pain management solutions remains a critical challenge, especially.amidst
:growing :concerns over the-use of conventional opioids. In the US,opioid-related mortality rates have
surged to as many as 80 deaths per 100,000 people in.some states,?-with an=estimated economic.
burden of USD: 1.5 trillion annually-exceeding the gross domestic product (GDP) of most US
industrial sectors A remarkable breakthrough lies in the discovery that indole and'oxindole,alkaloids,.:
•produced by several genera within the plant Tribe"Naucleeae act on opioid receptors without;
activating the beta-arrestin=2:pathway, the primary driver of respiratory depression and overdose'
deaths. This systematic review explores the'pharmacological properties, mechanisms of action,
2
dosing considerations, interactions, and long-term effects of mitragynine and corynoxeine, alkaloids
from the Southeast Asian plant Mitragyna speciosa (kratom) and others in the Tribe Naucleeae.
Mitragynine, a partial opioid receptor agonist, and corynoxeine, known for its anti-inflammatory and
neuroprotective effects, demonstrate significant therapeutic potential for managing diverse pain
types—including neuropathic, inflammatory, nociceptive, visceral, and central pain syndromes=with"
a focus on cancer pain. Unlike traditional opioids, these compounds do not recruit beta-arrestin-2,
avoiding key adverse"effects such as respiratory depression, severe constipation, and rapid tolerance
development. Their distinct pharmacological profiles make them innovative candidates for safer, non-
lethal pain relief. However, challenges persist including the unregulated nature of kratom products,
inconsistencies in potency due to crude extract variability, potential for misuse, and adverse drug
interactions. Addressing these issues requires establishing standardized quality control protocols,
such as Good Manufacturing Practices (GMP), to ensure consistent potency and purity. Clear.
labeling requirements with dosage guidelines and warnings should be mandated to ensure safe use
and prevent misuse. Furthermore, the implementation of regulatory oversight to monitor product
quality and enforce compliance is essential. This review emphasizes the urgency of focused research
to optimize dosing regimens, characterize the pharmacodynamic profiles of these alkaloids, and
evaluate long-term safety. By addressing these gaps, the mitragynine-and corynoxeine-related drug
classes can transition from promising plant-derived molecules to validated pharmacotherapeutic
agents, potentially revolutionizing the field of pain management.
Keywords: mitragynine, corynoxeine, pain management, Mitragyna speciosa, systematic review,
pharmacology, p-arrestin, opioids
1. Introduction
The search for effective pain management solutions remains a critical challenge, especially amidst
growing concerns over the side effects and dependency risks associated with conventional opioids. In
the United States, opioid misuse has led to significant mortality and economic burden, with opioid-
related deaths estimated at 80 per.100,000 individuals in some states and an annual cost of
approximately USD.1.5 trillion [1]. Amid this crisis, certain indole and oxindole alkaloids from the plant
tribe Naucleeae have emerged as promising alternatives due to their ability to engage opioid
receptors without activating the (3-arrestin-2 pathway, a key mediator of respiratory depression and
other severe opioid side effects [2]:
The alkaloid composition of Mitragyna speciosa (kratom) is dominated by mitragynine, which
constitutes approximately 66.2% of the total alkaloid content in commercial kratom products. In
contrast, 7-hydroxymitragynine, despite its higher potency at opioid receptors, is a minor component,
accounting for only 0.01-0.03% of the total alkaloids. Other significant alkaloids include
speciociliatine (8.6-16.6%), paynantheine (9.0-16:0%), and speciogynine (6.6-8.6%), with trace
amounts of additional alkaloids such as corynoxeine, isocorynoxeine, and speciophylline. These
secondary alkaloids may also contribute to kratom's pharmacological profile but in a less pronounced
manner. The variability in alkaloid composition across kratom products is influenced by factors such
as genetic differences, environmental conditions, and processing methods, resulting in
inconsistencies that affect their pharmacological effects and safety profiles.
Among these compounds, mitragynine and corynoxeine,derived from the Southeast Asian
plant Mitragyna speciosa (Figure 1), commonly known as kratom, stand out as potentially safer
alternatives to traditional opioids. While kratom contains a range of bioactive alkaloids, the oxindoles,
including corynoxeine and its`stereoisomer isocorynoxeine, are minor yet significant tetracyclic
oxindole alkaloids. Kratom also contains other active compounds, such as flavonoids, polyphenols,
3
and terpenoids, which contribute to the pharmacological effects of the raw plant products and crude
plant extract. These oxindoles also"occur in higher concentrations in other plants; such as species
within the Lingerie genus, further highlighting their pharmacological importance L]. Mitragynine, an
indole alkaloid, is recognized as a partial agonist of the mu-opioid receptor (MOR), whereas
corynoxeine demonstrates notable anti-inflammatory and neuroprotective properties. Unlike
conventional opioids, both mitragynine and corynoxeine lack 13-arrestin recruitment, which reduces
risks of adverse effects such as respiratory depression, constipation, and tolerance development [4].
This unique pharmacological profile positions them as promising candidates for managing various
types of pain-including neuropathic, inflammatory, nociceptive, visceral, and central pain
syndromes—with a particular focus on cancer-related pain:
:Figure 1.
_.._ __. ...........ta _Open in anew tab
Mitragyna speciosa, commonly known as kratom, contains bioactive secondary metabolites,
specifically indoles.(e.g., mitragynine) and oxindoles (e,g., corynoxeine):
This review focuses specifically on mitragynine and corynoxeine as representative compounds of the
indole and oxindole alkaloid classes, respectively. Although kratom is traditionally consumed in its
whole form (e.g., crude leaves or powdered leaves), isolating and examining these two compounds
allows for a targeted analysis of their unique therapeutic potential, mechanisms of action, and safety.
,profiles. By focusing on mitragynine and corynoxeine, this review seeks to reflect the broader
pharmacological potential of indole and oxindole alkaloids, addressing their potential applications in
pain management without the confounding factors present in whole-plant kratom formulations. For
4
reference, Table 1 and Table 2 present the principal structures of the oxindole and indole alkaloids
derived from Mitragyna speciosa; providing an overview of these compounds' structural diversity
relevant to their pharmacological profiles.
Table'I
Principal structures of oxindole alkaloids of Mitragyna speciosa..
0 =
3 Compound. ., „'.. R, ,a`'>!i 3 r-irrii1-2-6-17 f R-2
-:
,.
Corynoxeine H S R S R CHCH2
Corynoxine A H S S.-. S I` S " CH2CH3
Corynoxine B H S R S S CH2CH3
Mitrafoline OH S S S S CH2CH3
1_-. S eciofoline OH ," R R i S i S F' CH2CH3
Specionoxeine l : OCH3 S i R ; S !i R CHCH2
Rhynchophylline H S R S R CH2CH3
Rotundifoline OH S S S R CH2CH3
Rotundifoleine OH S S S R CHCH2
Open manew to
Table 2.:: . .
Principal;structures of indole alkaloids of Mitragyna speciosa. .
. Compound . `RI _- 3 ii" 15 20 RZ
Mitragynine OCH3 S S S CH2CH3
Speciogynine ," '" OCH3 S S " ! R CH2CH3 ;
Speciociliatine OCH3 R S S CH2CH3
Mitraciliatine ? OCH3 R . S R l ': CH2CH3
Paynantheine OCH3 S S R CHCH2
Corynantheidine OH S S S CH2CH3
5
p
0 en"in.a new-tab
Despite these"promising"pharmacological profiles,:challenges remain,:particularly around the
unregulated nature of kratom products, variability in dosage, and potential for abuse;This review
aims to identify and critically assess relevant studies to provide an in-depth understanding;of the ..
i gy • ry
current;evidence surrounding. nine mitre , co noxeme, :and other krafom-derived.alkaloids..While no
clinical trials have yet defined therapeutic doses or established guidelines, the preclinical and :.
observational.data reviewed here may offer preliminary insights that could inform future research:
This synthesis:is intended to support clinicians:and"researchers"in gaining a foundational
understanding of these compounds' potential pharmacological profiles and mechanisms, and to •
-encourage further investigation into their role in pain management and other therapeutic a1eas.
Policyrnakers and the general public may also find this review beneficial in understanding the.
:complex landscape of:kratom's benefits and risks as they:relate"to public health considerations..
::".""Results
2.1:. Pharmacodynamlcs
Corynoxeine's noxeine's mec i r s gg . g.. .p pain through
ry hanisms.of action su estai nificant:' otential in the treatment of ainthrou
several pathways
Anti-Inflammatory Agent: Corynoxeine's role-as an anti-inflammatory agent is critical in managing
pain linked to inflarrimation, a common.cause,in "conditions such:as arthritis and autoimmune:
diseases. Through inhibition of vascular smooth muscle cell (VSMC) proliferation, particularly by.
:blocking the extracellular signal-regulated kinase.(ERK1/2) phosphorylation pathway, corynoxeine
reduces inflammatory processes in vascular and tissue contexts: This"anti-inflammatory activity can " .
help mitigate pain by lessening the release of pro-inflammatory cytokines and mediators that.typically
;heighten pain.sensitivity; By targeting inflammation pathways, corynoxeine supports tissue health and
reduces the potential for chronic pain development
Neuroprotective Actions and Autophagy Enhancement:::Corynoxeine serves as a neuroprotective
agent, offering significant potential in-conditions associated with neuropathic pain where nerve cell
damage or dysfunction contributes to pain,perception:Through the enhancement of.autophagy, "
corynoxeine helps,clear neurotoxic protein.aggregates.such as alpha_synuclein, which can otherwise:
accumulate and cause neural stress and degeneration. By engaging pathways like Akt/mTOR to
:induce autophagy, corynoxeine may reduce neuronal death:and maintain nerve function, effectively
lowering pain signals associated with damaged or impaired nerves. This neuroprotective mechanism
could.be beneficial in conditions like peripheral neuropathyand neurodegenerative.diseases; where
nerve protection aligns ns with pain mitigation 6,7] -
:Calcium Channel Blockade and Vasorelaxation: Corynoxeine induces vasorelaxation by blocking L-
type calcium channels:in vascular smooth muscle cells, thus preventing the influx of calcium ions.. ..
Calcium'ions:playa critical:role in smooth muscle contraction; by limiting their:entry,'corynoxeine
reduces smooth muscle tone and relaxes blood vessels This vasodilation effect is.particularly;
:beneficial in conditions where vascular constriction is linked to pain,:such as migraines and certain
vascular pain syndromes. Enhanced blood;flow from:.reduced vascular resistance can alleviate ;
6
symptoms by improving oxygenation and nutrient delivery to affected tissues, thus reducing ischemic
or tension-induced pain [6,7,8].
Adrenergic Receptor Antagonism: By inhibiting a1A adrenergic receptors,.corynoxeine further
promotes vasodilation, countering the effects of adrenergic-mediated vasoconstriction. Adrenergic
receptors, when activated, increase vascular tone, which can exacerbate pain in conditions like
tension headaches and hypertension-related discomfort. Corynoxeine's.antagonism of these
receptors allows for relaxation of blood vessels,:which can ease pain by reducing the stress and
pressure within the vascular system. This mechanism adds a layer of vascular relief in pain conditions
where adrenergic activity contributes to vascular tightness and discomfort
Potassium Channel Activation and Vascular Smooth Muscle Relaxation: As a potential potassium
channel opener, corynoxeine hyperpolarizes vascular smooth muscle cells,_further reducing cellular
excitability and promoting vasodilation. The activation of potassium channels encourages the efflux of
potassium ions, stabilizing the cellular membrane potential away from depolarization thresholds that
trigger contraction. This action complements calcium channel inhibition, creating a dual mechanism
for smooth muscle relaxation. By decreasing vascular resistance and enhancing blood flow,
corynoxeine's potassium channel activation may help alleviate pain from vascular sources, as seen in
migraine and other vascular pain disorders 6,7 ..
Prevention of Vascular Smooth Muscle Cell Proliferation:s Corynoxeine also inhibits the proliferation of
vascular smooth muscle cells (VSMCs), an effect particularly relevant in conditions like
atherosclerosis and restenosis, where abnormal cell growth contributes to vascular narrowing and
pain. By blocking the ERK1/2 pathway, corynoxeine disrupts the signaling required for VSMC
proliferation, which can prevent or slow down the progression of vascular blockages: This mechanism
is essential in managing chronic pain linked to vascular diseases, as maintaining healthy,
unobstructed vessels can reduce ischemic pain and improve blood circulation to affected regions
[Z,8]
In summary, corynoxeine's multi-faceted mechanisms—including its roles as an anti-inflammatory
agent,:neuroprotective agent, calcium channel blocker, adrenergic receptor antagonist, and
potassium channel opener-highlight its potential in effectively managing and treating various types
of pain: :.
Mitragynine's mechanisms of actions also suggest significant potential in the treatment of pain but
through unique polypharmacologypathways (summarized in Figure 2).
Figure 2.
7
Open in a new tab
Polypharmacology of mitragynine, the principal indole alkaloid derived from Mitragyna speciosa.
Mu-Opioid Receptor (MOR) Partial Agonist: Mitragynine acts as a partial agonist at mu-opioid
receptors(MOR), which are primary targets for traditional opioid analgesics;With a binding affinity of
approximately 0.233 pM; mitragynine can activate MOR to produce analgesic effects but with limited
efficacy compared to full agonists like morphine. This partial agonism allows mitragynine to provide
pain relief while significantly reducing the side effects typically associated with opioid receptor
activation,.including respiratory depression and high.potential for addiction. The decreased abilitylo
fully activate MOR is linked to a reduced risk of tolerance development, meaning that patients are
less likely to need increasing doses over time to achieve the same level of pain relief. Additionally, the
partial agonism at MOR may result in lower risks of gastrointestinal side effects, such as constipation,
which is a common issue with traditional opioids
Kappa=Opioid Receptor (KOR) Antagonist: In .contrast to its partial agonism at MOR, mitragynine
functions as,an antagonist at kappa-opioid receptors_(KOR). KOR activation is often associated with
dysphoria, hallucinations,.and a reduction in reward-seeking behaviors. By antagonizing KOR,
mitragynine reduces these adverse effects, potentially providing mood-stabilizing effects and
lessening dysphoric reactions. KOR antagonism also contributes to pain relief, as KOR can play a
role in modulating pain perception, especially in conditions where stress and mood are exacerbated
8
by pain. This dual MOR.agonism and :KOR antagonism may offer a balanced analgesic effect while
avoiding some of the psychological side effects of KOR agonists [12]
Competitive Antagonist at Serotonin`Receptors(5-HT2A): Mitragynine acts asa competitive
antagonist at the 5-HT2A serotonin:receptor, which modulates the release of various
neurotransmitters involved in mood,cognition, and pain perception. By blocking 5-HT2A receptors,:
mitragynine can reduce serotonin-related neurotransmission, which may help in stabilizing mood and
controlling pain;perception, particularly in individuals with anxiety or depression-related pain. This
antagonism is also thought to reduce anxiety and prevent overstirnulation of neural pathways,
contributing to an improved quality of life for those with chronic pain.[9,10]: ,
Partial Agonist:at 5-HT1A: As a partial agonist at the 5-HT1A receptor, mitragynine can enhance
serotonin signaling to some extent,,particularly in".ways that are anxiolytic and mood-enhancing The
5-HT1A receptor is linked to.improved mood and anxiety reduction, both•of which are beneficial,in
chronic pain management, as pain can be exacerbated by psychological stress.and anxiety. By
partially activating this receptor, mitragynine may improve the psychological state of individuals
suffering from chronic pain, which indirectly aids:in pain management by reducing pain perception
linked to stress and anxiety [2,10].
p gy
Binding to 5-HT2B and 5-HT2C Rece tors:•Mitra nine.has weaker interactions with 5-HT2B and 5-
HT2C serotonin receptors, binding with a Ki of approximately 1260 nM: While these interactions are
less pronounced than its actions on other receptors, they may have'subtle modulatory effects on •
mood and cognition:.Since 5-HT2B and 5-HT2C receptors are involved in the regulation of mood and
appetite, the slight binding affinity could contribute to mitigating:symptoms like irritability or loss of
appetite in individuals with chronic pain, although the impact is likely minor compared to its effects on
other rece tors'L,10
p l
Alpha-2 Adrenergic Receptor Agonist: Acting as an agonist at alpha-2 adrenergic receptors,
mitragynine engages mechanisms similar to clonidine, a drug used to manage opioid withdrawal •
symptoms:Alpha-2 agonism can reduce norepinephrine release, which calms the sympathetic •
nervous system and provides a sense of relaxation and reduced arousal..This agonism is particularly,
useful for managing symptoms of opioid withdrawal, including cravings, irritability, and heightened
pain sensitivity. The activity at:alpha-2 receptors may also:contribute to the overall analgesic effect of.
mitragynine by reducing sympathetic responses that can intensify pain perception in stressful
situations [9,13]., •
Dopamine D2.Receptor Affinity: Mitragynine's affinity for dopamine D2 receptors suggests potential
antipsychotic effects, which may alleviate symptoms of psychosis in vulnerable individuals. By
interacting with D2 receptors, mitragynine could theoretically reduce excessive dopamine activity,
Which
h:is linked to conditions such as schizophrenia and bipolar disorder:.For.chronic.pain patients,
this dopaminergic modulation might help in managing pain perception-and emotional responses, as
well as.in mitigating the negative psychological symptoms sometimes associated with chronic pain,
such as anhedonia and low motivation 14
:receptor, whichAity: Unlike traditional opioids, mitragynine does not recruit p-arrestin 2 at the mu-opioid
Arrestin Activity:
p is significant because 6-arrestin 2 recruitment is linked to several adverse effects of
opioids„including respiratory:depression,:constipation,and tolerance j ]. The absence of(3-arrestin
9
• . gg potentially safer side ..
2 recruitment in mitragynine's mechanism•su ests a effect profile, offering
effective pain relief without the heightened risks associated with conventional opioids: This property is
a crucial factor:in its unique pharmacological Safety,:making it a promising candidate for further
research in pain management settings.
'Cannabinoid Receptor;Modulation: Mitragynine also interacts with cannabinoid receptors, particularly
CB1 .and CB2, which play roles in;modulating pain and inflammation Research,;indicates that
'mitragynine's analgesic effects, particularly in neuropathic pain, may mediated through;these
cannabinoid.pathways. For instance, in models of chemotherapy-induced peripheral neuropathy; the.
analgesic effect of mitragynine was lessened when cannabinoid receptors were blocked,'suggesting
that these receptors.are instrumental in its effect on neuropathic pain. This cannabinoid receptor
interaction provides a unique avenue for pain relief, especially in complex pain conditions involving
both central and peripheral mechanisms L]:
TRPV1 Modulation: Recent studiesihave shown that mitragynine may modulate the Transient
Receptor Potential,Vanillloid 1 receptor (1);a non-opioid pathway involved in sensing:noxious:stiimulli,
such as heat and inflammation. By affectingTRPV1 -receptors, mitragynine can potentially reduce
pain signaling in inflammatory and neuropathic pain conditions. TRPV1. modulation is particularly
relevant for pain states where peripheral sensitization occurs, as blocking or modulating these
receptors decreases the activation of pain pathways. This pathway represents an additional analgesic
mechanism that can complement its opioid-like effects LE].
The absence of significant Delta-Opioid Receptor (DOR) activity in both mitragynine and corynoxeine
indicates that their,analgesic and neuroprotective effects are mediated through other pathways:[12].
DORs.are involved in modulatin ain, mood, and neurop rotection, but:DOR agonists are associated
9p
with the risk of convulsions and other adverse effects.
2.2.,:Pharmacokinetic5
Mitragynine, the principal indole alkaloid.in Mitragyna speciosa (kratom), exhibits distinctive
pharmacokinetic properties that are crucial to its therapeutic applications: It is a lipophilic;weak base
(pKa :-'8.1) with high plasma protein binding (85-95%) and undergoes extensive hepatic metabolism.:
through both phase I (oxidation, demethylation). and phase II (glucuronidation; sulfation) pathways:
The pharmacokinetics of mitragynine demonstrate dose-dependent variations, with key parameters. ..
providing;insights into its behavior:After a single dose, the Cmax ranged from 17.1 ng/mL:(6.65 mg
dose) to 125 ng/mL (53.2 mg dose),while at steady-state (Cmax,ss), it ranged from 21.4 ng/mL to'
143 ng/mL:-The Tmax remained consistent across both single and multiple doses, ranging from:.1:0 to
1.7 h:The elimination half-life (t1/2) increased significantly with dose, ranging from 8.5 h at the:lowest
:dose<to 43:4.h at the highest dose for single dosing, and from 25.7 to.67.9 h at steady state. Systemic
exposure, measured as.AUCO-°°; increased proportionally with dose; ranging from 52.8 h•ng/mL to
;908 h•ng/mL,after a single;dose,while steady-state:AUC (AUCO—T,ss).ranged from 85.1 h.ng/mL to
'958.h•ng/mL.::Clearance (CL) decreased with,increasing doses, ranging from 278 L/h at lower doses
to94.L/h at higher doses, indicating nonlinear pharmacokinetics. The volume of distribution (Vd) also
:increased with dose,from1.349 L to'3788 L for single doses and from 2980. L to 6020 L at;steady
State,:reftecting extensive tissue:distributio DIE.:These findings highlight the importance;of.dose,.;_
adjustments.to account for significant Chan es in clearance and half-life at higher doses.
io
A significant factor influencing the pharmacokinetics of mitragynine is the variability between
administering pure mitragynine versus raw kratom products. Raw kratom contains a complex mixture
of alkaloids and bioactive compounds that can alter absorption, metabolism, and clearance, resulting
in greater variability in pharmacokinetic parameters. For instance, other alkaloids in raw kratom may
competitively inhibit or enhance mitragynine metabolism, affecting Cmax, Tmax, and t1/2.
;Furthermore, no standardization of kratom formulations or dosing exists, making it challenging to
establish predictable therapeutic outcomes or mitigate potential adverse effects.
The pharmacokinetics of corynoxeine exhibit notable differences between normal physiological
conditions and CUMS-induced depression models, which are essential to consider for therapeutic
applications. In normal rats,the maximum plasma concentration (Cmax) of corynoxeine'was 407.48 ±
10.87 ng/mL, with a time to reach Cmax (Tmax) of 1.67 ± 0.24 h. In contrast, CUMS-induced
depression rats demonstrated a lower Cmax of 306.83 ±.18.72 ng/mL and a delayed Tmax of 2.33 ±
0.47 h, indicating reduced absorption under pathological conditions. The elimination half-life(t1'/2)
was slightly longer in CUMS-induced depression rats (2.68 ± 0.30 h) compared to normal rats (2.40 ±
0.12 h), while the clearance rate (CL) was faster in the depression model (18.06 ± 1.36 L/h/kg versus
14.48 ± 0.61 L/h/kg in normal 'rats), suggesting a reduced systemic exposure to the compound [14].
Additionally, the volume of distribution (Vd) was significantly higher in CUMS-induced depression rats'
(69.15 ± 3.25 L/kg) compared to normal rats (50.09.± 2.11 L/kg), implying greater tissue penetration
inthe pathological state:The area under the concentration—time curve (AUC), representing overall
drug exposure, was reduced in'CUMS-induced rats;with.AUCO-t values of 1202.97 ± 39.79 ng-h/mL
versus 1495.62 ± 55.23 ng.h/mL in normal rats and AUCO-°° values of 1614.48 ± 119.62 ng.h/mL
versus.1914.65 ± 95.66 ng•h/mL, respectively (14]. These findings highlight a significant impact of
depression on corynoxeine's pharmacokinetics, including reduced absorption, faster clearance, and
greater distribution into tissues.
The altered pharmacokinetic parameters in the depression model underscore the influence of
pathological conditions on the behavior of corynoxeine within the body.These differences emphasize'
the need for tailored dosing regimens in clinical applications to ensure therapeutic efficacy and safety
in patients with underlying 'conditions. Understanding these variations provides a foundation for
optimizing the use of these compounds in different physiological and pathological contexts.
Furthermore; these disparities underscore the necessity of further research to optimize
standardization, characterize dose-response relationships, and establish regulatory frameworks for
the safe and effective clinical use of mitragynine and kratom products.
3. Discussion
3.1. Summary of Findings
Mitragynine and corynoxeine exhibit significant potential in effectively managing and treating various
types of pain through their multifaceted mechanisms,of action. When addressing pain management,
there is a large basis of pharmacotherapy because of the vastly diverse pathophysiology. While these
compounds hold significant potential in neuropathic pain (chemotherapy-induced peripheral;
neuropathy (CIPN), diabetic neuropathy, postherpetic neuralgia), inflammatory pain, nociceptive pain
(post-surgical, musculoskeletal), visceral pain (IBS, endometriosis), and central pain syndromes (MS,
spinal cord injury), cancer pain'is the most notable for effective'management. :
11
Cancer pain Presents'a unique challenge in pain :management due to its complex and multifaceted
nature, often involving a combinational nociceptive, neuropathic,.and inflammatory-components'. : : s:
Traditional opioids like morphine have long been the mainstay for cancer:pain management;
however, their use is associated with significant drawbacks, including the risk of.tolerance,
;dependence,:respiratory depression, and constipation. Furthermore, recent:studies.have suggested,
that morphine,and other opioids may promote tumor growth and metastasis by:enhancing
angiogenesis:and suppressing immune function:[1_9;20]:This potentially:adverse:effect on:cancer:
'progression highlights the need for alternative analgesics that do not compromise:,cancer treatment,
;outcomes. ::
Mitragynine and corynoxeine offer promising:alternatives to traditional opioids for cancer.pain
;management.Mitragynine, a partial agonist at mu-opioid receptors,:proviides effective analgesia while
reducing the risk of severe side effects associated with full opioid:agonists [16]: Its,lack of beta
arrestin.2::recruitment minimizes the risks of respiratory:depression, constipation, and tolerance
:development. Additionally, :mitragynine's partial agonist:activity at;5-HT1A receptors and antagonist,
activity,at 5-HT2A receptors may::offer mood-enhancing and anxiolytic benefits,:which are crucial for.
the overall well-being of cancer:patients[,21],
Corynoxeine, with its:potent anti-inflammatory and;neuroprotective:properties, can further enhance:..
pain f relie in cancer patients::Its ability to reduce"inflammation and protect neurons from:damage is
particularly beneficial in managing pain caused by tumor growth and metastasis [,22].;Corynoxeine's
vasorelexant effects, mediated.through calcium channel blocking:and adrenergic receptor
'antagonism, can help alleviate pain associated;with tumor-induced vascular tension and improve
blood flow to affected.tissues[,22].
Moreover; neither mitragynine nor corynoxeine has:been showh to promote tumor growth, making
them saferoptions for cancer patients compared to:traditional opioids [23,24]: By offering effective
analgesia without:the risk of enhancing tumor progression,:these compounds represent a:significant.
advancement in the management of cancer pain Th:e combined pharmacological actions of
mitragynine and corynoxeine;: including their;opioid receptor:modulation,.anti-inflammatory:effects
and_neuroprotective properties, position .them:as superior alternatives"to traditional:opioids like
morphine for cancer pain management. Their potential to provide comprehensive pain;relief while.
minimizing adverse effects and supporting overall patient health underscores'their importance in the
;evolving .landscape of cancer pain therapeutics:.
13-Arrestin Activity
:G-protein-coupled receptors such as the opioid receptors are transmembrane receptors that are.
capable of recruiting proteins.[i'arrestins to initiate separate cellular,signal transduction pathways
[12]::One of the most promising aspects of the..major alkaloids found in Mitragyna speciosa is their ;
lack'of.beta-arrestin 2:recruitment. Traditional opioids like'morphine and fentanyl not only activate
protein::signaling:pathways to provide pain relief but also recruitibeta-arrestin 2' This recruitment is ,
associated with many adverse effects, ::such as respiratory depression, constipation, and:the
development of tolerance and dependence..Beta-arrestin:2 mediates:these effects by desensitizing
the receptors, internalizing there,and initiating altern,
12
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