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Cannabis contains compounds that directly target cannabinoid receptors. Psychedelics like Lysergic Acid Diethylamide (LSD) target serotonin receptors. By acting through serotonin pathways, LSD affects endocannabinoid synthesis and function, according to a recent study published in the British Journal of Pharmacology.1

The October 2022 BJP study, featuring contributions from Dr. Vincenzo Di Marzo, Gabriella Gobbi, and several other scientists, sought to quantify serotonin and endocannabinoid-like molecules in the brains of mice that were sacrificed after a seven-day LSD regimen. Repeated 30 microgram doses of LSD per kilogram of body weight elicited anxiolytic and prosocial behavior. The researchers from Canada, Italy and Australia also examined how LSD affected the microbiome of the mice after the seven-day, 30-microgram dose routine.

The study noted anti-depressant and anti-anxiety effects triggered by LSD, which altered endocannabinoid tone and affected the serotonin metabolite, kynurenic acid, without impacting the levels of serotonin or its precursor tryptophan. Increased interaction among mice and anxiolytic behavior occurred, in part, through endocannabinoid signaling and corresponded to changes in a few key families of gut bacteria. These results were seen after repeated doses of LSD, not after a single session.

LSD Impacts Endocannabinoid Tone by Binding to Serotonin Receptors

Psilocybin, ayahuasca, mescaline, and LSD cause a psychedelic “trip” by binding to 5HT-2A, a serotonin receptor. This is one of 14 serotonin receptors, which induce a family of enzymes known as phospholipases (PLs). Various serotonin receptors induce different PLs. And two compounds (agonists) that activate the same receptor can promote different enzymes.

Serotonin receptors drive a symphony of endocannabinoid-producing PLs. Previous research has shown that serotonin facilitates the release of 2-AG, a major endocannabinoid, through a phospholipase c (PLC)- dependent mechanism.2 LSD and psilocin (the psychedelic metabolite of psilocybin) induce different PL enzymes by binding to the 5-HT2A receptor.

In recent years, psilocybin and MDMA have been explored as potential treatments for post-traumatic stress disorder, but somewhat more quietly so has cannabis. In fact, according to a few quick searches of PubMed, cannabis has a longer and richer association with PTSD in the scientific literature than any psychedelic. Though you wouldn’t know that by reading the headlines.

Setting aside for a minute how effective psychedelics may or may not be as breakthrough treatments for PTSD, there’s no doubt that cannabis is still much easier for most patients to access.

Recent research – including three new studies (from three different countries) – suggests that growing numbers of PTSD sufferers are medicating with cannabis, and truly finding it helpful.

Depression Drives Cannabis Use

First, a paper in the journal BMC Psychiatry1 from researchers based in Ontario, Canada, provides some insight into cannabis use among PTSD patients during the first wave of the coronavirus pandemic. Between April 3 and June 24 of 2020, 462 individuals with self-reported PTSD completed an online questionnaire that assessed mental health symptoms and cannabis intake both before the pandemic and in the seven days prior to filling out the survey.

Stress, anxiety, and depression worsened across the board, but by categorizing participants according to cannabis use patterns – not using, using less, using the same, or using more – the researchers discovered something interesting. PTSD sufferers who increased their cannabis use during the pandemic were more likely to also experience “meaningful perceived worsening of depression symptoms,” the authors write.

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We fight against the stigmatization of cannabis, as well as the snake-oil promoters that mislead consumers.

At Project CBD, we fight against the stigmatization of cannabis, as well as the snake-oil promoters that mislead consumers. When Fox News dredges up boogeyman claims that marijuana smoking causes gun violence, we counter with peer-reviewed evidence demonstrating the link between cannabis use and prosocial behavior. And when we see CBD and cannabis brands touting their products as “sleep aids” because they include CBN (cannabinol), we feel it’s our responsibility to let our readers know there’s actually no scientific basis for marketing claims that CBN has soporific properties.

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CBD has exploded in popularity over the past decade.

Ethan Nadelmann talks about the power and promise of this cannabinoid with one of the world’s leading experts on the subject: Martin A. Lee, author of two highly acclaimed books, Acid Dreams and Smoke Signals, and cofounder and director of ProjectCBD.org. The two cover various topics including what is CBD and how does it work, what is its relationship to THC and what’s the evidence for its medical and health benefits, what role is the FDA playing in regulating hemp and what’s going on outside the United States?

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