Is Cannabis a Psychedelic Drug?

Yes, and it may work via 5-HT2A as well as the cannabinoid receptors.

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Cannabis is a genus of plants (aka marijuana, hemp), not a drug, although the term is often used interchangeably. Recently, there has been an explosion in the terminology, abbreviations, and chemical names associated with cannabis. This can be confusing when trying to understand cannabis and how it works. To begin, here are a few terms to know and their definitions:

  • Cannabis – Also called marijuana or hemp. This is a genus of flowering plants that are indigenous to Central Asia and the Indian Subcontinent. Two of the most well-known species grown for their psychoactive effects are Cannabis sativa and Cannabis indica. To make hemp, C. sativa plants are grown to produce different strains that contain much lower levels of psychoactive chemicals. The psychoactive compounds in cannabis are most abundant in the buds (flowers) of the plant.
  • Cannabinoids (Figure 1) – This is a class of over 100 chemical compounds found in cannabis plants. Here are three of the most well-known:
    • Cannabinol (CBN) – A non-psychoactive compound that is not synthesized by the plant but is an oxidation breakdown product of most abundant cannabinoid, THC (see below). CBN does have some entourage effect when combined with THC, resulting in greater sedation effects. CBN has not been thoroughly studied but may it have antibiotic and anti-inflammatory properties.
    • Cannabidiol (CBD) – Another non-psychoactive compound in cannabis. CBD by itself is believed to have many health benefits and can be found in many over the counter products. CBD is also the active component in the recently FDA-approved epilepsy drug Epidiolex.
    • Tetrahydrocannabinol (THC) – This is the most abundant compound in cannabis and it is responsible for many of its euphoric and psychoactive effects.

Figure 1: The chemical structures of the cannabinoids THC, CBN, and CBD.

What is a Psychedelic Drug?

The term psychedelic was created by English psychologist and researcher Humphry Osmond. He derived it from the Greek words for mind or soul (psyche) and show (deloun) to describe the effect LSD had on the mind. Osmond first used the word in a presentation he gave at the New York Academy of Sciences in 1957.1

Basically, there are two ways to figure out if a drug is psychedelic. The first is based on its receptor binding. The second is to compare the effects of the drug to what are considered psychedelic effects. If a compound passes the test for either or both, then it is psychedelic.

In terms of receptors, scientists classify a drug as psychedelic if it binds to serotonin 5-HT2A receptors (5-HT2AR) as an agonist or partial agonist2–4 (these are typically tryptamine compounds which are chemically similar to serotonin). The hallucinogenic effects of agonist binding are mediated via the 5-HT2AR receptor-coupled signaling pathway.2,3 This pathway is not entirely understood, but researchers theorize that it involves activation of the enzyme phospholipase C leading to the formation of inositol phosphates and diglycerol (signaling molecules) which causes the release of calcium ions from the endoplasmic reticulum in the cell. The possibility also exists that other serotonin receptors may be involved in the overall psychedelic experience of a user.

Interestingly, the effects of psychedelic drugs are highly variable and may not be dose-dependent.4 With LSD, for example, low doses (about <100 µg) may cause some distortion of cognitive and sensory processes with the person remaining aware that the drug is causing the effects. Higher doses may “…transport the user to an alternate reality, where they lose contact with their everyday environment.” These are the transcendent or mystical experiences that represent states of consciousness that are profoundly altered from reality.

From a medical standpoint, it is now understood by researchers that having a mystical experience results in a dramatic improvement for patients using psychedelic-assisted therapy.5–8 However, the mystical phenomenon can occur when using almost any dose of a psychedelic as long as the set and setting have been optimized to promote an altered state of consciousness.4

THC and other compounds in cannabis that have been tested elicit their effects by binding as agonists or partial agonists on the cannabinoid receptors CB1 and CB2. Like the serotonin receptors, cannabinoid receptors belong to the G protein-coupled receptor (GPCR) family.

When it comes to 5-HT2AR, current research indicates THC binding may have a role in the development of schizophrenia in young adults with long-term cannabis use.9 This study found that in young mice, long-term exposure to THC “…induced a pro-hallucinogenic molecular conformation of the 5-HT2AR.” The researchers also observed “…exacerbated schizophrenia-like responses…” in the mice. These observations of the modification of 5-HT2AR by THC is not only a ground-breaking finding but it also adds to the evidence of cannabis being a psychedelic drug based on receptor binding.

Comparing the Effects of Cannabis and Psychedelics

Although the chemistry of the classic psychedelics and the compounds in cannabis are very different from each other, they have remarkably similar effects in many people.

In 1964, the iconic psychedelic researcher and advocate Timothy Leary, along with colleagues Ralph Metzner and Richard Alpert, developed a scale for measuring the intensity of a psychedelic experience.10 Based on its effects, they included marijuana as a psychedelic in their analysis. The researchers said the effects of moderate to high doses of cannabis included synesthesia, enhanced perception of music, visual effects (including patterns) with the eyes closed, the emergence of unconscious emotions, and unrestrained creative and abstract thought patterns. Many of these effects are common for users of psychedelics taken at low to moderate doses.

Taking higher doses of psychedelics results in out-of-body and mystical experiences for some users along with ego dissolution. Some experts think that cannabis can cause ego dissolution, too. Stephen Gray, editor, and contributor to the book “Cannabis and Spirituality: An Explorer’s Guide to an Ancient Plant Spirit Ally” told PotGuide in an interview that “Cannabis is both gentle and intense. If you take a large enough dosage to actually do that kind of work [achieve ego dissolution], it can be quite powerful.” Gray implies that the ability of cannabis to do this may have a lot to with a person’s intent (part of the set and setting) when taking it.

Summary

Experts consider cannabis a psychedelic drug in terms of its effects and possibly its binding to 5-HT2AR. New research is indicating that the psychedelic serotonin 5-HT2A receptor may play a role in the adverse effects of chronic cannabis use in adolescents. Although the psychedelic experience can be highly variable, cannabis and psychedelics, in general, have many effects in common.

Overall, it’s important to remember that both cannabis and naturally occurring psychedelics like psilocybin mushrooms (aka magic mushrooms) contain a cocktail of compounds, many of which have not been characterized. Further, understanding the entourage effect in cannabis and magic mushrooms may reveal other similarities in their receptor affinities and effects.

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Tellurikwaves

Well…i’m NOT an expert but though weed is gettin’stronger these days,and turn more and more minds into confused states of mind,t has not much to be compared to LSD

    References
  1. Osmond H. A Review of the Clinical Effects of Psychotomimetic Agents. Annals of the New York Academy of Sciences. 1957;66(3):418-434. doi:10.1111/j.1749-6632.1957.tb40738.x
  2. Nichols DE, Nichols CD. Serotonin Receptors. Chem Rev. 2008;108(5):1614-1641. doi:10.1021/cr078224o
  3. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38(8):1083-1152. doi:10.1016/S0028-3908(99)00010-6
  4. Nichols DE. Psychedelics. Pharmacological Reviews. 2016;68(2):264-355. doi:10.1124/pr.115.011478
  5. Garcia-Romeu A, R. Griffiths R, W. Johnson M. Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction. Current Drug Abuse Reviews. 2014;7(3):157-164. https://www.ingentaconnect.com/content/ben/cdar/2014/00000007/00000003/art00005.
  6. Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology. 2006;187(3):268-283. doi:10.1007/s00213-006-0457-5
  7. Griffiths R, Richards W, Johnson M, McCann U, Jesse R. Mystical-type experiences occasioned by psilocybin mediate the attribution of personal meaning and spiritual significance 14 months later. J Psychopharmacol. 2008;22(6):621-632. doi:10.1177/0269881108094300
  8. Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R. Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects. Psychopharmacology. 2011;218(4):649-665. doi:10.1007/s00213-011-2358-5
  9. Ibarra-Lecue I, Mollinedo-Gajate I, Meana JJ, Callado LF, Diez-Alarcia R, Urigüen L. Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway. Neuropsychopharmacol. 2018;43(10):2028-2035. doi:10.1038/s41386-018-0076-y
  10. Leary TF, Metzner R, Alpert R. The Psychedelic Experience: A Manual Based on the Tibetan Book of the Dead.; 1964.