Not Your Parents’ Pot: Cannabis Is More Potent Now

By Dr. Ty Schepis

Eventually, most adults reach a point where we realize we are out of touch with those much younger than us.

Perhaps it is a pop culture reference that sparks the realization. For me, this moment happened when I was in my late 20s and working with adolescents in school settings to help them quit smoking. When other drugs would occasionally come up, I didn’t understand some of the slang terms they used for these drugs. Many people may have that feeling now when the topic of cannabis comes up – especially in its different and newer forms.

As a professor of psychology, I focus my research on substance use in adolescents and young adults. A major change during my time in research is the legalization and explosion of cannabis availability across the U.S.

There are arguments for and against increasing legalization of cannabis for adult use in the U.S., but expanded access to legal cannabis also may have unintended consequences for adolescents. These consequences are compounded by the increasing potency of some cannabis products.

I use the word “cannabis” since it refers to the plant from which the drugs are derived. It also serves as a catch-all term for any substance with chemical compounds from cannabis plants and addresses concerns that the word marijuana has some long-standing racist overtones.

Cannabis now comes in a larger variety of forms than it used to. When most people over 40 think of cannabis, they imagine its dried form for smoking. This cannabis was not particularly strong: The average THC concentration of cannabis seized by the Drug Enforcement Agency in 1995 was 4%, while it was roughly 15% in 2021.

In addition to the smoked form, some might remember an edible form, often baked into a dessert like a brownie, or hashish, which is derived from more potent parts of the cannabis plant.

Today there are many different cannabis concentrates that have high levels of THC, typically ranging from 40% to 70%, and more than 80% in some cases, depending on the method of extraction. These include oils that can be vaporized by vape or dab pens, waxier substances and even powders.

Differences in Cannabis Products

THC and cannabidiol, or CBD, are the most common chemicals in cannabis. Each one interacts with the brain in different ways, producing different perceived effects.

CBD does not produce the same “high” that THC does, and cannabidiol may have benefits as a medication for severe epilepsy, as well as other potential but as yet unproven medical uses. The differences between THC and CBD come from how they interact with cannabinoid receptors – the proteins onto which these drugs attach – in the brain and body.

However, CBD can also make people sleepy, alter mood in unintended ways and cause stomach upset. Never use a CBD product without consulting a physician.

THC is the chemical most strongly associated with the high from cannabis. By increasing the amount of THC, concentrated products can increase blood levels of THC rapidly and more strongly than nonconcentrates such as traditional smoked cannabis.

Cannabis concentrates also come in many different forms that range from waxy or creamy to hard and brittle. They are made in a variety of ways that may require dry ice, water or flammable solvents such as butane.

The myriad names for cannabis concentrates can be confusing. Concentrate names include “budder,” which refers to a yellowish paste like frosting; “shatter” is made similarly to budder but comes in a thin, brittle and translucent form; there’s also “wax” or “crumble,” which confusingly is not waxy but is more like a powdery or grainy substance; and “keef” or “kief,” which is powdery in nature and derived from the most potent parts of the cannabis plant. It is similar to hashish.

The names change regularly and can vary by guide or from person to person. It is best to ask what a term means from an open and curious place than to act as if you know all the terminology.

Many concentrates are vaporized and inhaled. Vaporizing is different than smoking, as vaporizing heats the concentrate until it becomes a gas, which is inhaled. Smoking involves burning the compound to produce an inhaled gas.

Many who vaporize concentrates call it “dabbing.” This refers to the dab of concentrate to heat, vaporize and inhale. Another way to vaporize cannabis concentrates is to use a vape pen. Vape pens are sometimes also called dab pens, depending on the local terms.

Cannabis and Adolescents

One of the reasons why young people are drawn to these sorts of products is that vaping or dabbing the concentrated form makes it easier to hide cannabis use. Vaping cannabis does not create the typical smell associated with weed.

A 2021 systematic review found that past-year cannabis vaping nearly doubled from 2017 to 2020 in adolescents - jumping from 7.2% to 13.2%. A more recent study in five northeastern U.S. states found that 12.8% of adolescents vaped cannabis in the past 30 days, a more narrow time frame that suggests potential increases in use. In addition, a 2020 study found that one-third of adolescents who vape do so with cannabis concentrates.

Cannabis use by adolescents is scary because it can alter the way their brains develop. Research shows that the brains of adolescents who use cannabis are less primed to change in response to new experiences, which is a key part of adolescent development. Adolescents who use cannabis are also more likely to experience symptoms of schizophrenia, struggle more in school and engage in other risky behaviors.

The risks of cannabis use are even greater with concentrates because of the high levels of THC. This is true for both adolescents and adults, with greater risk for symptoms of schizophrenia such as hallucinations and delusions, mental health symptoms and more severe cannabis use.

The best analogy is with another drug – alcohol. Most people know that a 12-ounce beer is much less potent than 12 ounces of vodka. Cannabis in smoked form is closer to the beer, while a concentrate is more like the vodka. Neither is safe for an adolescent, but one is even more dangerous.

These dangers make early conversations with kids about cannabis and cannabis concentrates critically important. Research consistently shows that expressing disapproval of drug use makes adolescents less likely to start drug use.

Start these conversations early – ideally before middle school. You can find some helpful online resources to guide the conversation.

While these conversations can be uncomfortable, and you can look like the out-of-touch adult, they can be a major step toward preventing adolescents from using cannabis and other drugs.

Ty Schepis, PhD, is a Professor of Clinical Psychology at Texas State University. His research receives funding from the Food and Drug Administration and the National Institute on Drug Abuse.

This article originally appeared in The Conversation and is republished with permission.

Can Cannabis Help Prevent Dementia?

By Pat Anson, PNN Editor

People use cannabis for a variety of reasons. Some use it to relieve pain. Others use it to help them sleep, improve their appetite, or reduce anxiety and stress. Still others use cannabis because it makes them feel good.

A new study suggests there’s another unexpected benefit from consuming cannabis, especially when it’s used recreationally: It may help middle-aged adults ward of dementia.

Researchers at SUNY Upstate Medical University looked at health survey data that assessed the subjective cognitive decline (SCD) of over 4,700 U.S. adults between the ages of 45 and 64. Memory loss and confusion are symptoms of SCD, which is considered an early sign of dementia.

To their surprise, researchers found that participants who only used cannabis recreationally had significantly lower risk of SCD – as much as 96% less risk compared to non-users. Those who used cannabis for medical reasons or combined it with recreational use also had lower odds of SCD, but the difference was not statistically significant.

“We found that non-medical cannabis use was significantly associated with reduced odds of SCD in comparison to non-users. Several factors might explain this observation. Non-medical use of cannabis often contains THC, which has a psychoactive component that creates the ‘high’ sensation. Whereas CBD is non-psychoactive and often used for anxiety and chronic pain management,” the SUNY research team recently reported in the journal Current Alzheimer Research.

One likely reason for the disparity in SCD between recreational and medical users is that those who consume cannabis for health reasons may have comorbid medical conditions – such as diabetes, hypertension, cardiovascular disease and musculoskeletal disorders -- that raise their risk of dementia.

Another consideration is sleep. One of the primary reasons people use cannabis is to help them fall asleep faster and stay asleep longer. Recreational use of cannabis has the added benefit of improving sleep quality. A recent study found that insomnia is associated with a 51% higher risk of dementia risk.

The frequency of cannabis use and whether it was smoked, vaped or ingested had no significant connection to SCD risk.

Although the study found no direct cause-and-effect relationship between cannabis, SCD and dementia, researchers think it’s worth exploring further. More than six million Americans have Alzheimer’s disease or some form of dementia, a number that’s expected to double by 2050. 

“Despite the advancement of medicine and technology, dementia remains incurable and non-preventable. While some medications can slow symptom progression, they are only effective if started during early stages and cannot reverse its course,” SUNY researchers concluded. “Given the widespread use of cannabis in the U.S., it is imperative to pursue further research to understand the mechanism underlying the reduced odds of SCD among non-medical cannabis users.”

FDA Finds ‘Credible Scientific Support’ for Marijuana as Pain Reliever

By Pat Anson, PNN Editor

It took a lawsuit to prompt its release, but the U.S. Department of Health and Human Services (HHS) has finally made public a lengthy FDA review explaining why it thinks marijuana should be rescheduled as a Schedule III controlled substance. Such a move would make it legal under federal law for marijuana to be used for medically approved purposes, such as pain relief.

The FDA review was completed last August, nearly a year after it was requested by President Biden. But the 252-page review was not released until Friday, after a lawsuit was filed by two pro-cannabis lawyers when HHS didn’t respond to Freedom of Information Act (FOIA) requests.

Medical marijuana is already legal in 38 states, but cannabis remains classified as a Schedule I substance by the Drug Enforcement Administration, making its sale or use illegal under federal law. The DEA is expected to make its decision on rescheduling soon.

The FDA looked at seven potential medical uses of cannabis: pain, anorexia, anxiety, epilepsy, inflammatory bowel disease (IBD), nausea, and post-traumatic stress disorder (PTSD).

After reviewing clinical studies of cannabis, and the views of academic and professional medical societies, the FDA said they found “mixed findings of effectiveness.” The strongest evidence was for pain relief, anorexia and nausea.

The available data indicate that there is some credible scientific support for the use of marijuana in the treatment of pain.
— FDA review

“The largest evidence base for effectiveness exists for marijuana use within the pain indication (in particular, neuropathic pain),” the FDA said. “On balance, the available data indicate that there is some credible scientific support for the use of marijuana in the treatment of pain, anorexia related to a medical condition, and nausea and vomiting, with varying degrees of support and consistency of findings.”

Perhaps just as importantly, the FDA found no evidence of “unacceptably high safety risks” when marijuana was used therapeutically. That is a key finding for marijuana to be rescheduled by the DEA. The risk of marijuana being used nonmedically was also low, compared to substances like alcohol, heroin, cocaine, prescription opioids and anti-anxiety drugs.

“The rank order of the comparators in terms of greatest adverse consequences typically places heroin, benzodiazepines and/or cocaine in the first or immediately subsequent positions, with marijuana in a lower place in the ranking, especially when a utilization adjustment is calculated. For overdose deaths, marijuana is always in the lowest ranking among comparator drugs,” FDA said.

“These evaluations demonstrate that there is consistency across databases, across substances, and over time that although abuse of marijuana produces clear evidence of a risk to public health, that risk is relatively lower than that posed by most other comparator drugs.”

The FDA said the “vast majority” of professional medical organizations do not recommend marijuana, but they don’t specifically recommend against it either. The lone exception is the American Psychiatric Association, which warns that long-term use of marijuana can worsen psychiatric conditions, such as paranoia and hallucinations.

Reclassifying marijuana as a Schedule III substance – in the same category as codeine and ketamine – would certainly be historic, but it won’t resolve the many differences between federal and state regulation of cannabis.

Under federal law, legal access to Schedule III substances requires a prescription from a licensed doctor that is dispensed from a licensed pharmacy. Medical marijuana products would also have to go through the FDA’s lengthy and costly clinical trial process to assess their safety and effectiveness. Even if they pass that test, they would only be approved by FDA for certain conditions.  

Is It Safe for Doctors to Recommend Medical Cannabis?

By Dr. Joseph Parker

Nearly two-thirds of oncologists and pain management specialists say they are worried about the legal repercussions of recommending medical cannabis to their patients. This is not an unreasonable fear.

According to one survey, 60% of doctors fear professional stigma, and for good reason. I have seen colleagues call the DEA to report that a physician who certified patients for cannabis was selling marijuana from their office.  As absurd as this might seem, once the DEA gets rolling, they can always find an excuse to prosecute a physician treating pain or addiction. 

Cannabis may soon be moved from a Schedule I controlled substance, with no approved medical use, to a less restrictive Schedule III, where it would be regulated like codeine. This might relax some of those physicians, but I’m not sure it will.

There are many politicians and law enforcement officers who simply believe that marijuana is evil. The extreme was former Attorney General Jeff Sessions, who said at one time that marijuana was “only slightly less awful” than heroin. 

Sessions may truly believe this, but the comparison has no basis.  Heroin can cause respiratory depression and death.  Cannabis cannot.  Heroin works on the endorphin receptors in the brain to trigger a dopamine-mediated reward response, which can lead to what I call “true” addiction. 

Cannabis works predominately through the endocannabinoid system, though it can indirectly influence the release of dopamine and other brain areas associated with the reward system. That’s because the endocannabinoid system and CB1 receptors play a regulatory role in the release of various neurotransmitters, including dopamine.

When tetrahydrocannabinol (THC) binds to CB1 receptors, it can affect the release of dopamine and other neurotransmitters, which contributes to the pleasurable and rewarding effects associated with cannabis use.

I am not saying that someone cannot develop a cannabis substance use disorder or dependence. They certainly can, just like you can with caffeine, sugar or gambling, for that matter.  What I’m saying is that cannabis can make people feel good and want more, but it is nowhere near as dangerous as heroin.  It is also not neurotoxic, like methamphetamine, which can cause the death of brain cells with a single use. 

Some studies actually show a neuroprotective effect from cannabis. And, when taken by itself, cannabis cannot cause an overdose death. This is important. 

Every time the U.S. government targets something, they pay an army of statisticians to generate scary-sounding numbers. For example, you will hear claims that a rise in fatal car accidents was “associated” with cannabis. What exactly does that mean?  It means that a large percentage of accidents involve people who use cannabis, which is unsurprising since about 40% of the adult U.S. population has or is using cannabis.

Those same accidents show a much higher correlation with caffeine.  Caffeine use could be “associated” with probably 90% of all car accidents.  But correlation, of course, does not prove causation. 

These arguments present no evidence that cannabis caused the accidents.  However, the news media can get sloppy about scientific accuracy.  A study will say that a certain number of accidents “involved” cannabis, and the media will report that the cannabis “caused” the accident.

CBD vs. THC

For some reason, Sessions was also obsessed with CBD (cannabidiol). CBD is not THC, which is psychoactive and has a significant effect on a user’s mental processes.  CBD is considered non-psychoactive by a majority of experts, including the World Health Organization.

THC has a higher affinity for CB1 receptors, which are primarily found in the brain and central nervous system, and is a partial agonist for both CB1 and CB2 receptors. Activation of CB1 can cause euphoria and relaxation. It also alters sensory perception, impairs short-term memory, induces anxiety and paranoia, and impairs motor coordination.

CBD does not directly activate those receptors or have those effects. It is instead considered a negative allosteric modulator of CB1 receptors. CBD modifies the CB1 receptor response to THC and actually moderates some of the psychoactive effects of THC.  

There is also evidence that CBD can be anxiolytic and antipsychotic, while THC has been linked (not proven) to be associated with schizophrenia and psychosis.  THC can lead to the release of dopamine, which accounts for the euphoria, but at too low a level to be compared with more addictive substances.

CBD has been found in at least one study to be effective in the treatment of heroin addiction, and in another study to increased motivation, possibly giving us something to treat symptoms of schizophrenia.

Does this all mean it is safe to recommend cannabis to your patients?  Not really. While cannabis has been shown in several replicated studies to be helpful in the treatment of chronic pain, right now it is not safe for doctors to prescribe or recommend. 

Even in states where cannabis is legal for medical use and federal courts have upheld the right of physicians to recommend it, I would argue that the DEA takes a different view.

In the recent prosecution of a physician for “overprescribing” opiates, prosecutors claimed at a press conference that they started investigating the doctor after a call from local police regarding an overdose death.  Evidence later showed this was not the case.  The doctor was actually first targeted for agreeing to certify patients for their state’s medical cannabis program. 

You can help educate your patients about cannabis, but send them on to someone who does not prescribe controlled substances. Until physician rights are restored and protected in this country, it’s just not safe to recommend cannabis.

Joseph Parker, MD, is Chief Science Officer and Operations Officer at Advanced Research Concepts, a company developing solutions to the challenges of space travel and space-related medical issues.  In clinical practice, Dr. Parker specialized in emergency medicine and served as Director of Emergency Medicine at two hospitals. Prior to that, he had a distinguished career in the U.S. Marines and Air Force. 

In 2022, a federal jury convicted Dr. Parker on two counts of unlawful opioid prescribing. He has filed an appeal as he awaits sentencing.

Rescheduling Won’t End Conflict Between Federal and State Marijuana Laws 

By Paul Armentano, Guest Columnist 

Ten months after the Biden administration requested the Department of Health and Human Services (HHS) “to initiate the administrative process to review expeditiously how marijuana is scheduled under federal law,” Secretary Xavier Becerra confirmed that the agency has recommended cannabis be removed from its Schedule I classification and placed in a lower schedule.

While the explicit details of HHS’ recommendation are not public, Bloomberg reports that the agency seeks to have cannabis moved to the less restrictive Schedule III of the federal Controlled Substances Act. 

The HHS recommendation now goes to the Drug Enforcement Administration, which will conduct its own scientific review. In the past, the DEA has employed its own five-factor test (which differs from HHS’ criteria) to determine whether or not cannabis ought to be rescheduled. On four prior occasions, most recently in 2016, the agency determined that cannabis failed to meet any of its five criteria.  

While it remains unknown at this time how the DEA will ultimately respond to HHS’ request, many are already speculating about the potential implications of such a policy change. And while some entities, particularly those involved in the commercial cannabis industry, have lauded the proposed change as a “giant” step forward, others – like myself – have been far more restrained.

That’s because reclassifying cannabis from Schedule I to Schedule III is neither intellectually honest, nor does it sufficiently address the widening chasm between state and federal marijuana laws. 

Specifically, reclassifying cannabis to a lower schedule within the CSA continues to misrepresent the plant’s safety relative to other controlled substances such as oxycodone and hydrocodone (Schedule II), codeine and ketamine (Schedule III), benzodiazepines (Schedule IV), or alcohol (unscheduled). More importantly, rescheduling marijuana fails to provide states with the explicit legal authority to regulate it within their borders as best they see fit, free from federal interference.  

To date, 38 states regulate the production and distribution of cannabis products for medical purposes. Twenty-three of these states regulate the possession and use of marijuana for adults. All of the state laws are currently in conflict with federal marijuana laws. Rescheduling cannabis to Schedule III will not change this reality. 

That’s because Schedule III substances are regulated only for prescription use by the federal government. That means legal access to these substances is limited to patients who possess a prescription from a licensed physician and who have obtained the product from a licensed pharmacy.

Currently, no state government regulates cannabis in such a manner – nor is it likely that any state will reconstruct their existing laws and regulations to do so in the future. 

Simply put, if marijuana is rescheduled, state laws authorizing citizens to possess cannabis for either medical or social purposes will continue be in violation of the federal law, as would the thousands of state-licensed dispensaries that currently serve these markets. And the DEA would still possess the same authority it has now under federal law to crack down on these state-regulated markets should it elect to do so. 

Some have suggested that rescheduling the cannabis plant may provide greater opportunities for investigators to conduct clinical research into its eventual drug development, but this result is also unlikely. That is because many of the existing hurdles to clinical cannabis research, such as the limits placed upon scientists’ access to source materials, are marijuana-specific regulations and predate cannabis’ Schedule I classification.

Other impediments, such as requiring the US Attorney General to approve marijuana-specific research protocols are statutory and are not specific to marijuana’s scheduling in the CSA. 

For these reasons, the National Organization for the Reform of Marijuana Laws (NORML) holds the position that the only productive outcome of the current scheduling review would be a recommendation to deschedule cannabis – thereby removing it from the Controlled Substances Act altogether and providing states with greater discretion to establish their own distinct marijuana policies. (A case in point: In 2018 Congress removed from the CSA hemp plants containing no more than 0.3 percent THC, as well as certain cannabinoids derived from them.)

Descheduling would remove the threat of undue federal intrusion in existing state marijuana programs and would respect America’s longstanding federalist principles allowing states to serve as “laboratories of democracy.”

By contrast, rescheduling simply perpetuates the existing contradictions between state and federal cannabis laws, and it fails to provide any necessary legal recognition from the federal government to either the state-licensed cannabis industry or those adults who use the plant responsibly in compliance with state laws.

Paul Armentano is the Deputy Director for NORML, the National Organization for the Reform of Marijuana Laws.

HHS to DEA: Marijuana Is Not Heroin

By Pat Anson, PNN Editor

The top U.S. health agency is asking the Drug Enforcement Administration to reclassify marijuana as a Schedule III drug under the Controlled Substances Act, putting cannabis in the same risk category as codeine, ketamine and steroids. Marijuana is currently classified as a Schedule I substance, the same as heroin and LSD.  

Bloomberg News was first to report that a top administrator in the Department of Health and Human Services (HHS) wrote a letter to DEA Administrator Anne Milgram asking for the change. Although 38 states and the District of Columbia have legalized recreational or medical marijuana, it remains illegal under federal law.

President Biden asked HHS Secretary Xavier Becerra nearly a year ago to review marijuana’s legal status, saying the classification of marijuana on the same level as heroin “makes no sense” and that people shouldn’t go to jail for marijuana possession.

“I can now share that, following the data and science, @HHSGov has responded to @POTUS’ directive to me for the Department to provide a scheduling recommendation for marijuana to the DEA. We’ve worked to ensure that a scientific evaluation be completed and shared expeditiously,” Becerra posted on Twitter Wednesday.

Although the Biden administration favors the move, rescheduling will not be a slam dunk. Marijuana falls under the jurisdiction of the Department of Justice, not HHS, and Milgram reports to Attorney General Merrick Garland, not Becerra. Conservative states where marijuana remains illegal are also likely to oppose the move.

Rescheduling has long been the goal of marijuana advocates, but some are disappointed that HHS is recommending it be moved to Schedule III, where it will still be regulated as a controlled substance.

“The goal of any federal cannabis policy reform ought to be to address the existing, untenable chasm between federal marijuana policy and the cannabis laws of the majority of US states. Rescheduling the cannabis plant to Schedule III of the US Controlled Substances Act fails to adequately address this conflict,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group.

“Just as it is intellectually dishonest to categorize cannabis in the same placement as heroin, it is equally disingenuous to treat cannabis in the same manner as anabolic steroids. The majority of Americans believe that cannabis ought to be legal and that its hazards to health are less significant than those associated with federally descheduled substances like alcohol and tobacco. Like those latter substances, we have long argued the cannabis plant should be removed from the Controlled Substances Act altogether.”

The DEA will now conduct its own scientific review of marijuana. On at least four previous occasions, the DEA has refused to reschedule marijuana because there were inadequate safety studies and little scientific evidence supporting its use.

Another major hurdle under federal regulations is that before a substance can be used for a medical purpose, its “chemistry must be scientifically established to permit it to be reproduced in dosages which can be standardized.” That would imply that cannabis or pharmaceutical companies would need to produce marijuana medication in measured doses that are FDA approved and only available by prescription.

There is little consistency in labeling, regulating or testing of cannabis.products sold in states where it is legal. Many products are mislabeled, with concentrations of CBD (cannabinoids) and THC (tetrahydrocannabinol) that are well above or below their label claims.

“It will be very interesting to see how DEA responds to this (HHS) recommendation, given the agency’s historic opposition to any potential change in cannabis’ categorization under federal law,” said Armentano. “Since the agency has final say over any rescheduling decision, it is safe to say that this process still remains far from over.”

Although nearly a third of U.S. adults with chronic pain have used cannabis as a pain reliever, professional medical associations have been reluctant to endorse its use. In 2021, the International Association for the Study of Pain (IASP) released a position statement saying it could not endorse the use of cannabinoids to treat pain, citing too many “uncertainties” about the clinical evidence.

Veterans Say Cannabis Reduces Drug Use and Improves Quality of Life

By Pat Anson, PNN Editor

The U.S. Department of Veterans Affairs (VA) and the Department of Defense (DoD) have long taken a dim view of medical cannabis. VA providers are not allowed to recommend or prescribe cannabis, and veterans who admit using cannabis will have it recorded in their VA medical records, which could potentially lead to drug testing or “adjustments” in their treatment plans.

Despite those barriers, cannabis use among U.S. military veterans is growing. In a 2019-2020 survey, nearly 12% of veterans reported using cannabis, with younger veterans (20.2%) and those with psychiatric conditions (24%) even more likely to be cannabis users.

A new study helps explain the popularity of cannabis among veterans. In an anonymous survey of 510 veterans who use medical cannabis, 91 percent said it improved their quality of life and nearly half said it helped them reduce their use of over-the-counter and prescription drugs, including opioids, anti-depressants, muscle relaxers and anti-inflammatory medication.

Veterans who were Black, female, served in combat, and those with chronic pain were most likely to report a desire to reduce their use of “unwanted” medications.

“Many of the respondents reported that medicinal cannabis treatment helped them to experience a greater quality of life, fewer psychological symptoms, fewer physical symptoms, and to use less alcohol, fewer medications, less tobacco, and fewer opioids,” researchers reported in the journal Clinical Therapeutics.

“These findings should inform clinicians who work with the veteran population, as cannabis may be an effective means of helping veterans, especially women and racially minoritized members of this population, to reduce unwanted medication use.”

Previous research has suggested that medical cannabis may play a “harm reduction role” by helping people reduce or even stop their use of opioid pain medication. But a recent study found otherwise. In an analysis of prescription data for over 150,000 chronic pain patients, researchers found that opioid prescribing declined only slightly in states after medical marijuana was legalized.

The VA is also holding the line against using cannabis as a treatment for post-traumatic stress disorder (PTSD).  While many veterans use cannabis to relieve symptoms of PTSD and several states consider PTSD an approved use of medical cannabis, the VA maintains that “cannabis can be harmful,” especially when used long-term, and is “not recommended for the treatment of PTSD.”

Our Bodies Produce Chemicals Similar to THC in Cannabis  

By Drs. Prakash and Mitzi Nagarkatti, University of South Carolina

Over the past two decades, a great deal of attention has been given to marijuana – also known as pot or weed. As of early 2023, marijuana has been legalized for recreational use in 21 states and Washington, D.C., and the use of marijuana for medical purposes has grown significantly during the last 20 or so years.

But few people know that the human body naturally produces chemicals that are very similar to delta-9-tetrahydrocannabinol, or THC, the psychoactive compound in marijuana, which comes from the Cannabis sativa plant. These substances are called endocannabinoids, and they’re found across all vertebrate species.

Evolutionarily, the appearance of endocannabinoids in vertebrate animals predates that of Cannabis sativa by about 575 million years.

It is as if the human body has its own version of a marijuana seedling inside, constantly producing small amounts of endocannabinoids.

The similarity of endocannabinoids to THC, and their importance in maintaining human health, have raised significant interest among scientists to further study their role in health and disease, and potentially use them as therapeutic targets to treat human diseases.

THC was first identified in 1964, and is just one of more than 100 compounds found in marijuana that are called cannabinoids.

What Are Endocannabinoids?

Endocannabinoids were not discovered until 1992. Since then, research has revealed that they are critical for many important physiological functions that regulate human health. An imbalance in the production of endocannabinoids, or in the body’s responsiveness to them, can lead to major clinical disorders, including obesity as well as neurodegenerative, cardiovascular and inflammatory diseases.

We are immunologists who have been studying the effects of marijuana cannabinoids and vertebrate endocannabinoids on inflammation and cancer for more than two decades. Research in our laboratory has shown that endocannabinoids regulate inflammation and other immune functions.

A variety of tissues in the body, including brain, muscle, fatty tissue and immune cells, produce small quantities of endocannabinoids. There are two main types of endocannabinoids: anandamide, or AEA, and 2-arachidonoyl glycerol, known as 2-AG. Both of them can activate the body’s cannabinoid receptors, which receive and process chemical signals in cells.

One of these receptors, called CB1, is found predominantly in the brain. The other, called CB2, is found mainly in immune cells. It is primarily through the activation of these two receptors that endocannabinoids control many bodily functions.

The receptors can be compared to a “lock” and the endocannabinoids a “key” that can open the lock and gain entry into the cells. All these endocannabinoid receptors and molecules together are referred to as the endocannabinoid system.

The cannabis plant contains another compound called cannabidiol, or CBD, which has become popular for its medicinal properties. Unlike THC, CBD doesn’t have psychoactive properties because it does not activate CB1 receptors in the brain. Nor does it activate the CB2 receptors, meaning that its action on immune cells is independent of CB2 receptors.

Endocannabinoids Help Us Feel Better

The euphoric “high” feeling that people experience when using marijuana comes from THC activating the CB1 receptors in the brain.

But when endocannabinoids activate CB1 receptors, by comparison, they do not cause a marijuana high. One reason is that the body produces them in smaller quantities than the typical amount of THC in marijuana. The other is that certain enzymes break them down rapidly after they carry out their cellular functions.

However, there is growing evidence that certain activities may release mood-elevating endocannabinoids. Some research suggests that the relaxed, euphoric feeling you get after exercise, called a “runner’s high,” results from the release of endocannabinoids rather than from endorphins, as previously thought.

The endocannabinoids regulate several bodily functions such as sleep, mood, appetite, learning, memory, body temperature, pain, immune functions and fertility. They control some of these functions by regulating nerve cell signaling in the brain. Normally, nerve cells communicate with one another at junctions called synapses. The endocannabinoid system in the brain regulates this communication at synapses, which explains its ability to affect a wide array of bodily functions.

Research in our laboratory has shown that certain cells of the immune system produce endocannabinoids that can regulate inflammation and other immune functions through the activation of CB2 receptors.

In addition, we have shown that endocannabinoids are highly effective in lessening the debilitating effects of autoimmune diseases. These are diseases in which the immune system goes haywire and starts destroying the body’s organs and tissues. Examples include multiple sclerosis, lupus, hepatitis and arthritis.

Chronic Pain Linked to Low Levels of Endocannabinoids

Recent research suggests that migraine, fibromyalgia, irritable bowel syndrome, post-traumatic stress disorder and bipolar disease are all linked to low levels of endocannabinoids.

In a 2022 study, researchers found that a defect in a gene that helps produce endocannabinoids causes early onset of Parkinson’s disease. Another 2022 study linked the same gene defect to other neurological disorders, including developmental delay, poor muscle control and vision problems.

Other research has shown that people with a defective form of CB1 receptors experience increased pain sensitivity such as migraine headaches and suffer from sleep and memory disorders and anxiety.

We believe that the medicinal properties of THC may be linked to the molecule’s ability to compensate for a deficiency or defect in the production or functions of the endocannabinoids.

For example, scientists have found that people who experience certain types of chronic pain may have decreased production of endocannabinoids. People who consume marijuana for medicinal purposes report significant relief from pain. Because the THC in marijuana is the cannabinoid that reduces pain, it may be helping to compensate for the decreased production or functions of endocannabinoids in such patients.

Deciphering the role of endocannabinoids is still an emerging area of health research. Certainly much more research is needed to decipher their role in regulating different functions in the body.

In our view, it will also be important to continue to unravel the relationship between defects in the endocannabinoid system and the development of various diseases and clinical disorders. We think that the answers could hold great promise for the development of new therapies using the body’s own cannabinoids.

Prakash Nagarkatti, PhD, and Mitzi Nagarkatti, PhD, are Professors of Pathology, Microbiology and Immunology at the University of South Carolina. They receive funding from the National Science Foundation and the National Institutes of Health.

This article originally appeared in The Conversation and is republished with permission.

The Conversation

DEA Considers Synthetic THC Illegal  

By Pat Anson, PNN Editor

The Drug Enforcement Administration considers a synthetic form of THC — the psychoactive compound in cannabis and hemp — a controlled substance that is illegal under federal law.

Hemp was legalized federally under the 2018 Farm Bill, in part because hemp contains only trace amounts of THC. However, some companies developed a synthetic form of hemp-derived THC — called THC acetate ester (THCO) — to give consumers an intoxicating effect. Because THCO was modeled after the THC found in hemp, they claimed it could be legally sold and consumed.

However, in a recent letter to Rod Kight, an attorney who specializes in cannabis law, the head of the DEA’s Drug & Chemical Evaluation Section said the agency considers delta-8 and delta-9 products containing THCO to be Schedule I controlled substances, which are illegal to sell or possess.

“Delta-9-THCO and delta-8-THCO do not occur naturally in the cannabis plant and can only be obtained synthetically, and therefore do not fall under the definition of hemp. Delta-9-THCO and delta-8-THCO are tetrahydrocannabinols having similar chemical structures and pharmacological activities to those contained in the cannabis plant,” the letter states.

Kight said he’s been telling clients and personal friends that THCO is potentially dangerous.

“Although I do not always agree with the DEA’s view on cannabis matters, I agree with this opinion and, frankly, am not surprised,” he wrote.  “It has always been my view that THCO is a controlled substance under federal law. Although it can be made from cannabinoids from hemp, THCO is not naturally expressed by the hemp plant. It is a laboratory creation that does not occur in nature, at least not from the hemp plant.”

As Kight points out in his blog, the DEA letter does not address delta-8 or delta-9 THC, which are natural and derived from hemp. Although those substances are considered legal at the federal level, over a dozen states have banned products containing them.

In states where they remain legal, delta-8 and 9 are widely available in candy, gummies, cookies, tinctures and beverages. Some companies claim the products have “uniquely potent effects on pain” and other health conditions, even while admitting there is little evidence to support those claims.

The FDA became so alarmed by the profusion of delta-8 and delta-9 THC products — and their marketing to children — that it sent letters to five companies in 2022 warning them to stop making unsubstantiated medical claims.

"These products often include claims that they treat or alleviate the side effects related to a wide variety of diseases or medical disorders, such as cancer, multiple sclerosis, chronic pain, nausea and anxiety," FDA Principal Deputy Commissioner Janet Woodcock, MD, said in a statement. "It is extremely troubling that some of the food products are packaged and labeled in ways that may appeal to children.”

The FDA says it had received over 100 reports of adverse events involving delta-8 THC, with poison control centers reporting over 2,300 cases, including one that involved the death of a child.

Florida Study Blames Cannabis for Hundreds of Deaths

By Pat Anson, PNN Editor

Advocates of medical marijuana – or cannabis use in general – have long said you can’t overdose on cannabis and that the natural plant is even “safer than many foods.”   

But researchers at Florida Atlantic University say cannabis products – particularly synthetic cannabis – are riskier than many people believe. In a study recently published in the Journal of Nursing Scholarship, they called cannabis “a legitimate public health concern” that has killed hundreds of Floridians in recent years.  

Analyzing 2014 to 2020 data from the Florida Department of Law Enforcement, researchers found that 386 people died as a result of drug intoxication caused by cannabis use. It’s important to note that the vast majority of those deaths (98.7%) involved accidents such as motor vehicle crashes, with a handful of deaths caused by murder or suicide. No overdoses were reported.

Most of the Florida deaths also involved other substances such as alcohol, opioids, heroin and cocaine. In nearly two-thirds of the deaths, synthetic cannabinoids such as K2 or Spice were involved. Synthetic cannabinoids are chemicals sprayed onto dried, shredded leaves that mimic the effect of cannabis, but are often quite stronger.  

“Synthetic cannabinoids are part of the new psychoactive substances that are two to 100 times more potent than THC, the main psychoactive compound in marijuana,” said lead author Armiel Suriaga, PhD, an assistant professor in FAU’s College of Nursing.

Suriaga and his colleagues found that over 13 percent of those who died had cardiac-related conditions such as high blood pressure, atherosclerosis, cardiac arrhythmias or an enlarged heart. There was one death from an ischemic stroke and one death from a hemorrhagic stroke, both related to synthetic cannabis use.

“The persistent deaths from cannabis and synthetic cannabis use are a legitimate public health concern,” said Suriaga. “The public should remain vigilant of the adverse health outcomes associated with these substances and their unpredictable effects, especially for men who are disproportionately affected, and particularly for people with underlying cardiovascular and respiratory conditions.”

‘Misleading and Sensational’ Study

Marijuana advocates say it was unfair of the researchers to include synthetic cannabis in their study, which was funded by the National Institutes on Drug Abuse and the American Association of Colleges of Nursing. 

“To lump in adverse effects from synthetically produced compounds in this analysis is misleading and sensational, as these products are not cannabis and their safety profile is not at all comparable to that of natural cannabis,” said Paul Armentano, Deputy Director of NORML.

“Cannabis is psychoactive and that is why advocacy groups opine in favor of its regulation, including the imposition of age controls and product testing for purity and potency. Adverse effects from cannabis, like dysphoria (anxiety), are possible but are best mitigated by regulation and education — not by criminal prohibition.”

Previous studies have looked at the relationship between cannabis and motor vehicle accidents, with mixed results. A survey of people in Michigan who used medical marijuana for chronic pain found that over half had driven while under the influence of cannabis, and one in five say they've driven while “very high.”

Other studies found a decrease in traffic fatalities in states that legalized medical marijuana. That may be because patients were substituting cannabis for alcohol and other drugs used to relieve their symptoms.

Medical Cannabis Reduced Opioid Use in High Dose Patients

By Pat Anson, PNN Editor

In recent years, there have been several studies and surveys – most of them anecdotal -- suggesting that cannabis reduces the need for opioid pain medication. A large new study takes that research a step further, finding direct evidence that chronic pain patients, including those on high doses, significantly reduced their opioid use once they started using medical cannabis.

Researchers with the New York State Department of Health and University of Albany School of Public Health followed over 8,100 patients on long-term opioid therapy (LOT) after they began using medical cannabis. All of the patients had been on opioids for at least 120 days, including some on relatively high daily doses of 90 or more morphine milligram equivalents (MME).

Researchers found that average daily doses declined significantly over time, especially for patients on high opioid doses. After eight months of using medical cannabis (MC), patients taking over 90 MME saw their daily doses fall by nearly 70 percent, compared to a 29% reduction in those getting 50 to 90 MME and a 15% reduction in those on 50 MME or less.

“This cohort study found that receiving MC for longer was associated with opioid dosage reductions. The reductions were larger among individuals who were prescribed higher dosages of opioids at baseline. These findings contribute robust evidence for clinicians regarding the potential benefits of MC in reducing the opioid burden for patients receiving LOT and possibly reduce their risk for overdose,” researchers reported in JAMA Network Open.

The study has some weaknesses. Researchers did not track the pain levels of patients or the types of pain conditions they suffered from. Also unknown is the dose or types of cannabis products they consumed.   

Although the study was conducted at a time when patients nationwide were losing access to opioids or having their doses reduced, researchers say it is “highly unlikely” that impacted their findings because the dosage decline for their patients didn’t begin until they started consuming cannabis.  

Marijuana advocates cheered the study findings.  

“The relationship between cannabis and opioid use is among of the best-documented aspects of marijuana policy,” Paul Armentano, Deputy Director of NORML, said in a statement. “In short, the science demonstrates that marijuana is a relatively safe and effective pain reliever — and that patients with legal access to it consistently reduce their use of prescription opioid medications.” 

A similar study of over 500 chronic pain patients being treated at medical cannabis clinics found a significant decline in their pain levels. And 85% of patients reported they either reduced or stopped using opioids.

A Third of Chronic Pain Sufferers Used Cannabis for Pain Relief

By Pat Anson, PNN Editor

Nearly a third of U.S. adults (31%) with chronic pain have used cannabis as an analgesic, according to a new survey that found over half of those who used cannabis said it enabled them to decrease their use of opioid medication and other pain therapies.

The survey findings, published JAMA Network Open, involved 1,724 people with chronic non-cancer pain who live in the 36 states (and Washington DC) that have legalized medical marijuana.

Unlike other studies that only focused on cannabis reducing opioid use, this survey found that over half of pain sufferers using cannabis also reduced or stop using non-opioid prescription pain relievers and over-the-counter analgesics. Many respondents also reported decreasing their use of physical therapy (39%), cognitive behavioral therapy (26%) and meditation (19%).  

“Most persons who used cannabis as a treatment for chronic pain reported substituting cannabis in place of other pain medications including prescription opioids,” wrote lead author Mark Bicket, MD, an Assistant Professor in the Department of Anesthesiology, University of Michigan School of Medicine.

“The high degree of substitution of cannabis with both opioid and nonopioid treatment emphasizes the importance of research to clarify the effectiveness and potential adverse consequences of cannabis for chronic pain. Our results suggest that state cannabis laws have enabled access to cannabis as an analgesic treatment despite knowledge gaps in use as a medical treatment for pain.”

The survey did not ask whether respondents smoked, vaped or ingested cannabis products, so there’s no way to tell which method was more effective at reducing pain. Nevertheless, it adds to a growing body of evidence that cannabis reduces pain and helps pain sufferers decrease their use of medications and other therapies.  

“Cannabis has established efficacy in the treatment of multiple conditions, including chronic pain, and it possesses a safety profile that is either comparable or superior to other controlled substances,” said Paul Armentano, Deputy Director of NORML, a marijuana advocacy group.

“So it is no wonder that those with legal access to it are substituting cannabis in lieu of other, potentially less effective and more harmful substances. As legal access continues to expand, one would expect the cannabis substitution effect to grow even more pronounced in the future.”

Several previous studies have also found that cannabis users often reduce their use of prescription opioids. A large survey conducted last year found that most medical marijuana users either stopped (42%) or reduced (37%) their use of opioids. A small number were also able to stop using psychiatric medications for anxiety, depression and PTSD.  

Another recent study at Cornell University found that legalization of recreational marijuana in 11 states led to significantly reduced prescribing for Medicaid patients for a broad range of medications used to treat pain, depression, anxiety, seizures and other health conditions.

A 2021 Harris Poll found that twice as many Americans are using cannabis or CBD to manage their pain than opioids.

Why Cannabis Holds Promise for Pain Management

By Benjamin Land, University of Washington Center for Cannabis Research

Drug overdose deaths from opioids continue to rise in the U.S. as a result of both the misuse of prescription opioids and the illicit drug market.

But an interesting trend has developed: Opioid emergency room visits drop by nearly 8% and opioid prescriptions are modestly lower in states where marijuana is legalized.

Marijuana is produced by the cannabis plant, which is native to Asia but is now grown throughout the world. Individuals use marijuana for both its psychoactive, euphoria-inducing properties and its ability to relieve pain.

Chemicals produced by the cannabis plant are commonly known as cannabinoids. The two primary cannabinoids that occur naturally in the cannabis plant are THC – the psychoactive compound in marijuana – and CBD, which does not cause the sensation of being high.

Many marijuana users say they take it to treat pain, suggesting that readily available cannabinoids could potentially be used to offset the use of opioids such as morphine and oxycodone that are commonly used in pain treatment. A safer, natural alternative to opioid painkillers would be an important step toward addressing the ongoing opioid epidemic.

Intriguingly however, research suggests that cannabis use could also lessen the need for opioids directly by interacting with the body’s own natural opioid system to produce similar pain-relief effects.

I am a neuropharmacology scientist who studies both opioids and cannabinoids as they relate to pain treatment and substance abuse. My research focuses on the development of drug compounds that can provide chronic pain relief without the potential for overuse and without the tapering off of effectiveness that often accompanies traditional pain medications.

How Opioids Work

Our bodies have their own built-in opioid system that can aid in managing pain. These opioids, such as endorphins, are chemicals that are released when the body experiences stress such as strenuous exercise, as well as in response to pleasurable activities like eating a good meal. But it turns out that humans are not the only organisms that can make opioids.

In the 1800s, scientists discovered that the opioid morphine – isolated from opium poppy – was highly effective at relieving pain. In the last 150 years, scientists have developed additional synthetic opioids like hydrocodone and dihydrocodeine that also provide pain relief.

Other opioids like heroin and oxycodone are very similar to morphine, but with small differences that influence how quickly they act on the brain. Fentanyl has an even more unique chemical makeup. It is the most powerful opioid and is the culprit behind the current surge in drug overdoses and deaths, including among young people.

Opioids, whether naturally produced or synthetic, produce pain relief by binding to specific receptors in the body, which are proteins that act like a lock that can only be opened by an opioid key.

One such receptor, known as the mu-opioid receptor, is found on pain-transmitting nerve cells along the spinal cord. When activated, mu-receptors tamp down the cell’s ability to relay pain information. Thus, when these opioids are circulating in the body and they reach their receptor, stimuli that would normally cause pain are not transmitted to the brain.

These same receptors are also found in the brain. When opioids find their receptor, the brain releases dopamine – the so-called “feel-good” chemical – which has its own receptors. This is in part why opioids can be highly addicting. Research suggests that these receptors drive the brain’s reward system and promote further drug-seeking. For people who are prescribed opiates, this creates the potential for abuse.

Opioid drugs, which include heroin, oxycodone and fentanyl, are highly addictive.

Opioid receptors are dynamically regulated, meaning that as they get exposed to more and more opioids, the body adapts quickly by deactivating the receptor. In other words, the body needs more and more of that opioid to get pain relief and to produce the feel-good response. This process is known as tolerance. The drive to seek more and more reward paired with an ever-increasing tolerance is what leads to the potential for overdose, which is why opioids are generally not long-term solutions for pain.

How THC and CBD Relieve Pain

Both THC and CBD have been shown in numerous studies to lessen pain, though – importantly – they differ in which receptors they bind to in order to produce these effects.

THC binds to cannabinoid receptors that are located throughout the central nervous system, producing a variety of responses. One of those responses is the high associated with cannabis use, and another is pain relief. Additionally, THC is believed to reduce inflammation in a manner similar to anti-inflammatory drugs like ibuprofen.

In contrast, CBD appears to bind to several distinct receptors, and many of these receptors can play a role in pain reduction. Importantly, this occurs without the high that occurs with THC.

Because they target different receptors, THC and CBD may be more effective working in concert rather than alone, but more studies in animal models and humans are needed.

Cannabinoids may also be helpful for other conditions as well. Many studies have demonstrated that cannabinoid drugs approved for medical use are effective for pain and other symptoms like spasticity, nausea and appetite loss.

Along with the pairing of THC and CBD, researchers are beginning to explore the use of those two cannabinoids together with existing opioids for pain management. This research is being done in both animal models and humans.

These studies are designed to understand both the benefits – pain relief – and risks – primarily addiction potential – of co-treatment with cannabinoids and opioids. The hope would be that THC or CBD may lower the amount of opioid necessary for powerful pain relief without increasing addiction risk.

For example, one study tested the combination of smoked cannabis and oxycontin for pain relief and reward. It found that co-treatment enhanced pain relief but also increased the pleasure of the drugs. This, as well as a limited number of other studies, suggests there may not be a net benefit.

However, many more studies of this type will be necessary to understand if cannabinoids and opioids can be safely used together for pain. Still, using cannabinoids as a substitution for opioids remains a promising pain treatment strategy.

The next decade of research will likely bring important new insights to the therapeutic potential of cannabinoids for chronic pain management. And as marijuana legalization continues to spread across the U.S., its use in medicine will undoubtedly grow exponentially.

Benjamin Land, PhD is a Research Associate Professor of Pharmacology at the University of Washington School of Medicine and the UW Center for Cannabis Research. Land receives funding from the National Institutes of Health for cannabinoid research, and has received cannabinoid related funding from the University of Washington Addiction and Drug Abuse Institute and SCAN Design Foundation.

This article originally appeared in The Conversation and is republished with permission.

The Conversation

Smoking Marijuana More Effective Than CBD Extracts for Back Pain

By Pat Anson, PNN Editor

One of the reasons many medical marijuana users prefer edibles over smoking is that they are perceived as healthier.  Marijuana smoke contains many of the same chemicals and carcinogens as cigarette smoke, and could have harmful effects on people with respiratory or cardiovascular problems.

But a small new study conducted in Israel found that smoking marijuana is better than ingesting it, at least when it comes to treating chronic lower back pain. Researchers enrolled 24 adults with MRI or CT scans that showed evidence of disc herniation or spinal stenosis, and had them try two different types of cannabis treatment.

The first was a cannabis extract rich in cannabidiol (CBD), which was taken sublingually under the tongue daily for 10 months. After a month of no treatment, the same group smoked cannabis flowers rich in tetrahydrocannabinol (THC) up to four times a day for 12 months. Participants were allowed to take pain medication as needed, including oxycodone and acetaminophen.

The study findings, published in the Rambam Maimonides Medical Journal, showed there was little to no improvement in back pain when participants took the extract, but significant improvement when they smoked cannabis. The use of analgesic drugs also dropped significantly while smoking.

Notably, three patients dropped out of the extract phase of the study because it wasn’t helping them, but then returned to participate in the smoking phase.

“The current study is the first, to our knowledge, to indicate that THC-rich smoked therapy is more advantageous in ameliorating LBP (lower back pain), than low THC CBD-rich sublingual extracts. Despite the small number of patients, our data indicate that THC-rich smoked therapy is helpful in mitigating LBP,” researchers reported.

The most commonly reported adverse events during the study were nausea, dizziness, drowsiness and fatigue during the extract phase; sore throat and drowsiness were reported during the smoking phase. All of the adverse symptoms disappeared after a dose tolerance was reached. Most of the adverse effects were in female patients.

A 2019 study of medical marijuana users also found that smoking cannabis provided more pain relief than ingesting it. Over 3,300 people logged their symptoms on a mobile app while using a variety of cannabis products, including dried flower, edibles, tinctures and ointments. Smoking the dried flower provided more pain relief than any other cannabis product, regardless of the amount of THC.

Another problem with CBD edibles is that they are frequently mislabeled. A recent study of 80 CBD oils found that only 43 had concentrations of cannabidiols that were within 10% of their label claims – an accuracy rate of just 54 percent.

Lab Mice Agree: Delta-8 Just Like Taking Delta-9

By Pat Anson, PNN Editor

Laboratory mice at a research facility have figured out something that Congress failed to do when it legalized hemp in 2018: the tetrahydrocannabinol (THC) found in hemp can get you just as high as the THC found in marijuana.

That finding, in a new study led by researchers at the University of Connecticut, undermines one of the tenets of the 2018 Farm Bill, which made it possible for U.S. farmers to grow hemp again as a cash crop. The thinking at the time was that since hemp contained less than 0.3% tetrahydrocannabinol, the main psychoactive ingredient in marijuana, it couldn’t be used to get high.

The mice found otherwise. When given Delta-8 THC derived from hemp twice a day for five days, the mice showed signs of lethargy, dependence and “liking” behavior. Although not as potent as the Delta-9 THC derived from marijuana, researchers reported in the journal Drug and Alcohol Dependence that Delta-8 had similar psychoactive effects on the mice, “including evidence of dependence and abuse potential.”

“So they’re telling us the same thing people buying the stuff in gas stations tell us: (Delta-8) feels like THC,” says Steve Kinsey, PhD, a UConn School of Nursing professor and director of the Center for Advancement in Managing Pain.

Kinsey and his colleagues say Delta-8 and Delta-9 molecules are similar and act in the same way on the body. But while Delta-9 is illegal under federal law, Delta-8 is legally being sold in a wide array of edibles, beverages, tinctures and other products. Because they are made with CBD and THC derived from hemp, they can be purchased without an ID or marijuana prescription – even in states where medical or recreational marijuana is illegal.  A recent study found that some hemp-based edibles have 360% more THC than those sold in cannabis dispensaries.

“It’s creating a fight between marijuana and hemp” growers, says John Harloe, an attorney on a Colorado taskforce that is trying to address the different chemical variations of THC and their hazy legal status.

“(Marijuana) must be sold through dispensaries and pay high taxes, while hemp producers can sell essentially the same product but without the same regulations, due to the ambiguity in the Farm Bill,” Harloe said in a statement.

The Food and Drug Administration has been slow to regulate CBD products, but earlier this year the agency sent the first warning letters to companies for selling products containing Delta-8. The letters don’t take issue with Delta-8’s legal status, but focus instead on its unauthorized marketing as a treatment for chronic pain, nausea, anxiety and even cancer.