Psychedelics – A Topsy-Turvy Trip Through Time

-Written by Dr. Shreyjit Kaur

For most of the 1950s and early 1960s, hallucinogens such as LSD and psilocybin were regarded as “wonder drugs” for treating various psychiatric conditions such as mood disorders, anxiety, PTSD, and alcoholic addiction etc. As these became affiliated with the 1960s hippy counterculture, and anecdotes and narratives about “bad trips” and “psychotic breaks” began to emerge, the excitement around these novel drugs gave way to stigma, moral dread and panic. In addition to this, the fear of misuse and abuse, lead to psychedelics being outlawed globally; putting a dead end to any kind of further medical research. Still, their recreational use as ‘rave or club drugs’ has been quite prevalent, albeit behind closed doors. Because of the taboo associated with the use of psychedelics; and despite their relative safety, their therapeutic usage is contentious in the medical community.

But the sands of time are reversing and the once banished psychedelic drugs are again captivating the interest and curiosity of the researchers worldwide. 

“Psychedelic” drugs are a group of substances with diverse pharmacological properties that all have significant effect on conscious experience i.e., they induce altered thoughts and sensory perceptions. There are two broad categories of psychedelic drugs – “classic psychedelics” and “entactogens.” 

The classic psychedelics exert their primary effects as agonists at the 5-HT2A receptor (e.g., lysergic acid diethylamide [LSD], psilocybin, dimethyltryptamine [DMT] and mescaline). A lot of these substances are either found or are close analogues of chemicals found in plants or fungi, used traditionally for thousands of years in spiritual, sacramental, folk healing and shamanic rituals in different parts of the world, such as the ergot fungus (Claviceps purpurea), morning glory (Turbina corymbosa), peyote cactus (Lophophora williamsii), and the ayahuasca brew (Banisteriopsis caapi and Psychotria viridis). Entactogens are the second class of psychedelic drugs, which include methylenedioxymethamphetamine (MDMA), infamously known as “Ecstasy” or “Molly”, which functions predominantly as a serotonin-releasing agent and has effects that overlay but are markedly different from classic psychedelics. Other drugs categorized as “psychedelic” include ketamine (a dissociative anesthetic), scopolamine (an anticholinergic), and ibogaine (a substance with a complex neuropharmacology).

Observational studies involving members of Brazilian religious groups who regularly consume ayahuasca sacramentally; has revealed that, when compared to a comparable control group, long-term regular ayahuasca drinkers have a lower prevalence of substance use, structural brain changes that do not indicate obvious pathology, and better neuropsychological performance and psychosocial adaptation.

Currently, psychedelics are holding a great promise in the field of psychiatry as the new emerging psychotherapy. Psilocybin-assisted psychotherapy for addiction treatment in tobacco and alcohol dependence is extensively studied with positive outcomes. It also shows remission of symptoms in patients with treatment resistant major depressive disorder and obsessive-compulsive disorder.  Psilocybin and LSD-assisted psychotherapy have the potential to reduce the anxiety associated with terminal illness. MDMA-assisted therapy is also being researched as a treatment for social anxiety in adults with autism and to treat chronic treatment-resistant post-traumatic stress disorder. Various exploratory studies have found a profound and lasting positive effect of psychoactive substances (e.g., LSD, psilocybin, psychedelic tryptamines) on patients afflicted with chronic and acute migraines and cluster headaches. A hypothesis pertaining to their use in chronic pain is also established. There is also a significant interest in using psychedelic drugs in palliative/hospice care as these drugs can help patients overcome their fear of death and make their experience of dying more meaningful and spiritual.

Following a 50-year hiatus, the recent research has been promising enough to fill significant information voids; by addressing the mechanisms of action of psychedelics in terms of their effects on receptor subsystems, systems-level brain activity and connectivity, and cognitive and emotional processing. Furthermore, functional investigations have demonstrated that modifications in self-experience, emotional processing, and social cognition may contribute to their potential therapeutic impacts. Thus, giving out a scientific roadmap for the study and use of psychedelic drugs in the near future for some of humanity’s scariest health conditions.

References:

1. Tupper KW, Wood E, Yensen R, Johnson MW. Psychedelic medicine: a re-emerging therapeutic paradigm. CMAJ. 2015 Oct 6;187(14):1054-1059. doi: 10.1503/cmaj.141124. Epub 2015 Sep 8. PMID: 26350908; PMCID: PMC4592297.
2. https://www.health.harvard.edu/blog/back-to-the-future-psychedelic-drugs-in-psychiatry-202106222508#:~:text=Psychedelic%20drugs%20are%20a%20loosely,contain%20the%20active%20ingredient%20psilocybin.
3. Grob CS, McKenna DJ, Callaway JC, et al. Human psychopharmacology of hoasca, a plant hallucinogen used in ritual context in Brazil. J Nerv Ment Dis 1996;184:86–94. 
4. Bouso JC, Palhano-Fontes F, Rodríguez-Fornells A, et al. Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans. Eur Neuropsychopharmacol 2015;25:483–92.
5. Bouso JC, González D, Fondevila S, et al. Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of ayahuasca: a longitudinal study. PLoS ONE 2012;7:e42421.
6. Vollenweider FX, Preller KH. Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders. Nat Rev Neurosci. 2020 Nov;21(11):611-624. doi: 10.1038/s41583-020-0367-2. Epub 2020 Sep 14. PMID: 32929261.