"The larger the island of knowledge, the longer the shoreline of wonder."    Ralph Sockman

                      "It's important to keep an open mind, but not so open that your brains fall out."

Recent research suggests that psychedelics, when combined with psychotherapy, may be very helpful for a number of difficult-to-treat psychological disorders.  There are evidence-based reasons for suspecting these drugs may also have value in some general population settings.  In this post I introduce the variety of compounds that may be described as 'psychedelics' and give a brief background history of their use.  In subsequent posts, I will look at "Recent psychedelic research: their use in psychotherapy (1st post)", "Their use in psychotherapy (2nd post)", "How do they work?", "What are the risks?", "Their use in the general population", "Psychedelics and end of life distress", "Re-mining personal experience", "Lessons from current personal experience" and "Recent psychedelic research: further exploration".

I have written about psychedelics before on this blog, but my current interest was partly triggered by Michael Pollan's rather wonderful new book "How to change your mind" with its subtitle "What the new science of psychedelics teaches us about consciousness, dying, addiction, depression, and transcendence".  That's rather a big set of topics and maybe a big set of claims, but I think Michael delivers excellently with his exploration of these areas.  He has produced the best book I've ever read about psychedelics.  A lot of other people seem to agree with me as the book has apparently gone to the top of the New York Time hardcover, non-fiction bestsellers list (I believe it's scheduled to come out as a paperback in the UK at the end of May '19).  To quote some of the critics: "His approach is steeped in honesty and self-awareness.  His cause is just, his thinking is clear, and his writing is compelling." (Washington Post); "Gripping and surprising ... Pollan makes losing your mind sound like the sanest thing a person could do." (New York Times); and "There seems little doubt these drugs have far more to offer psychiatry than has been acknowledged." (Sunday Times).  Here is a good YouTube discussion of the book with Michael Pollan & Sam Harris.

I say my current interest was "partly triggered" by Michael Pollan's book.  The other, bigger trigger is the emerging research evidence.  I already have 200 or so recently published academic articles in my personal database.  The ten-stop timeline on COMPASS's website gives a good tour through some of the developing publication list - including early papers on the subjective effects of psychedelics and also their use in existential distress linked to advanced cancer, smoking cessation, alcohol dependence, OCD, and treatment-resistant depression.  However there's a big wave of developing research and any at-this-point-in-time position statement is rapidly overlaid with new, additional knowledge.  Recently, whole editions of academic journals have been devoted to psychedelics ... see, for example, the 10 papers in July's edition of the Journal of Psychopharmacology,  the 21 papers in November's "Psychedelics: New doors, altered perceptions" edition of Neuropharmacology, the 26 papers in Frontiers in Pharmacology's current research topic "Psychedelic drug research in the 21st century" and the 6 review papers in this autumn's "The renaissance in psychedelic research" edition of International Review of Psychiatry.  The latter began with an editorial titled "Psychiatry might need some psychedelic therapy". 

So what are 'psychedelics'?  In their recent paper "Classic psychedelics: An integrative review of epidemiology, mystical experience, brain network function, and therapeutics", the authors Matthew Johnson (from John Hopkins) & colleagues write "Perhaps the best description of a classic psychedelic is found in Grinspoon and Bakalar (1979, page 9) who define it as 'A drug which, without causing physical addiction, craving, major physiological disturbances, delirium, disorientation, or amnesia, more or less reliably produces thought, mood, and perceptual changes otherwise rarely experienced except in dreams, contemplative and religious exaltation, flashes of vivid involuntary memory, and acute psychosis.' Classic psychedelics often cause extreme changes in subjective experience during acute drug action, encompassing complex changes in affective, cognitive, and perceptual domains. One type of subjective experience referred to as mystical-type experience can be occasioned by administration of relatively high doses of classic psychedelics in optimal settings ... The term “hallucinogen,” which has been widely applied to classic psychedelics in scientific circles, is not ideal because these substances do not typically produce frank hallucinations, and this term, which connotes only perceptual effects, is an insufficient description of the often radical effects these drugs have on human consciousness and one’s sense of self. Therefore, the term “hallucinogen” has fallen out of favor, with a re-emergence of the scientific use of the term “psychedelic” to refer to these substances. The term “psychedelic,” which means “mind-manifesting” was coined by the pioneering classic psychedelic researcher Humphrey Osmond in 1957 ... recent psychological and biological research indicates the accuracy of this term by suggesting this class of drugs to cause a non-ordinary and more variable form of consciousness that is less centered on one’s normal sense of self, and that involves enhanced autobiographical recollection."

These authors also comment "Classic psychedelics fall within one of two general structural categories. One category includes variations on the structure of tryptamine. Examples include LSD, psilocybin, and dimethyltryptamine (DMT), a psychoactive compound present in the South American sacramental beverage ayahuasca. The second category includes variations on the structure of phenethylamine. One example is mescaline, the main psychoactive agent in the peyote (Lophophora williamsii), San Pedro (Echinopsis pachanoi) and Peruvian torch (Echinopsis peruvianus) cacti. A variety of synthetic compounds not known to occur in nature also fall in the phenethylamine category (e.g., 2C-B, 25I-NBOMe). Indigenous cultures in the Western Hemisphere have used compounds from both structural classes in the sacramental use of ayahuasca, psilocybin-containing mushrooms, and mescaline-containing cacti. One analog of phenethylamine is methylenedioxymethamphetamine (MDMA), which causes psychoactive effects with only partial overlap with classic psychedelics, and which works primarily via serotonin release rather than 5-HT2AR agonism. Like MDMA, other drugs sometimes labelled as psychedelic (e.g., NMDA antagonists, anticholinergics, cannabinoids, salvinorin A, ibogaine) which are not classic psychedelics, will not be reviewed here because of their substantially differing mechanisms and effects."   For more on these "non-classic" agents see links in this Wikipedia article on psychedelics. 

What's the 'history' of psychedelics?  As noted in the paragraph above, sacramental use of ayahuasca, psilocybin-containing mushrooms, and mescaline-containing cacti dates back thousands of years.  In fact, in their paper "Prehistoric peyote use", the authors used radiocarbon dating on archaeological peyote button specimens and noted - "The identification of mescaline strengthens the evidence that native North Americans recognized the psychotropic properties of peyote as long as 5700 years ago."   And other investigators have both extended our understanding of the extensiveness of psychedelic use and pushed back still further how long these sacred/healing rituals have gone on for - see "Hallucinogenic drugs in pre-Columbian Mesoamerican cultures" and "Iconography in Bradshawb rock art: breaking the circularity".  In a 2018 paper - "Psychedelics: Where we are now, why we got here, what we must do" - Belouin & Henningfield write "The purpose of this commentary is to provide an introduction to this special issue of Neuropharmacology with a historical perspective of psychedelic drug research, their use in psychiatric disorders, research-restricting regulatory controls, and their recent emergence as potential breakthrough therapies for several brain-related disorders. It begins with the discovery of lysergic acid diethylamide (LSD) and its promising development as a treatment for several types of mental illnesses during the 1940s. This was followed by its abuse and stigmatization in the 1960s that ultimately led to the placement of LSD and other psychedelic drugs into the most restrictively regulated drug schedule of the United States Controlled Substances Act (Schedule I) in 1970 and its international counterparts. These regulatory controls severely constrained development of psychedelic substances and their potential for clinical research in psychiatric disorders. Despite the limitations, there was continued research into brain mechanisms of action for psychedelic drugs with potential clinical applications which began during the 1990s and early 2000s. Finding pathways to accelerate clinical research in psychedelic drug development is supported by the growing body of research findings that are documented throughout this special issue of Neuropharmacology. Accumulated research to date suggests psychedelic drug assisted psychotherapy may emerge as a potential breakthrough treatment for several types of mental illnesses including depression, anxiety, post-traumatic stress disorder, and addiction that are refractory to current evidenced based therapies. This research equally shows promise in advancing the understanding of the brain, brain related functioning, and the consequential effects of untreated brain related diseases that have been implicated in causing and/or exacerbating numerous physical disease state conditions. The authors conclude that more must be done to effectively address mental illnesses and brain related diseases which have become so pervasive, destructive, and whose treatments are becoming increasingly resistant to current evidenced based therapies. This article is part of the Special Issue entitled ‘Psychedelics: New doors, altered perceptions’."

See too further posts on "Recent psychedelic research: their use in psychotherapy (1st post)", "Their use in psychotherapy (2nd post)", "How do they work?", "What are the risks?", "Their use in the general population", "Re-mining personal experience" and "Recent psychotherapy research: further exploration".