In recent years there have been countless headlines about new clinical research involving psychedelic drugs, trumpeting advances in a manner akin to: ‘New Study Shows Progress in LSD Research – Offers new potential for treatment of’ – a google search of “Recent LSD research” will provide a gratifying demonstration. Indeed, three new review articles about psychedelic drugs, place emphasis on milestone developments (1, 2, 3).
Some high profile media aggrandizement of the ‘powerful potential of psychedelics’ may indeed help to propel future studies, but what about the enormous Stigma that also surrounds psychedelic drugs? Can it simply be dismissed as “hysteria?” Is talk of mind control, bad trips, acid casualties and flashbacks all poppycock? Since it’s first semi-synthesis in 1947 by Albert Hoffman, LSD has always been thought of as having “powerful potential.” But without careful science, a new-wave Stigma may be brought about. Indeed, science by definition takes phenomena, studies them and by revealing their nature makes them more predictable. The effects of psychedelic drugs, are still defined as being largely unpredictable and potential danger remains lurking. Before going on to use them in a clinical setting and keeping our fingers crossed, a large dose of basic science could provide much needed insight. Insight that actualizes all this “potential” for therapeutic use.
Psychedelic drug research: At it’s worst
Interest in the potential of psychedelic drugs increased sharply after the oft-written about, accidental ingesting of LSD tartrate in 1943 that made for Albert Hoffman’s unforgettable “kaleidoscopic and fantastic” bicycle trip home from the Basel Sandoz laboratories in Switzerland. As outlined in a review from last month, it wasn’t long before LSD was semi-synthesized en masse for the production of Delysid – sugar-coated tablets for administration. It found itself largely in the hands of experimental psychiatrists, and psychologists treating depression, alcoholism, schizophrenia and autism. These experiments were reported to provide “therapeutically valuable insights into unconscious processes.” Between 1953 and 1973 there were a reported 116 studies involving psychedelic drugs, all funded by the US government. There existed an enthusiasm that smacks of familiarity with the current zeitgeist.
Soon after Hoffman’s trip, in 1951, the Central Intelligence Agency began it’s MKUltra program; the birth of the “problem child” of psychedelic research – a term used by Albert Hoffman himself. Alongside research with more ethical motivations the MKUltra program was officially concerned with mind control – behaviour modification and prisoner interrogation. Experiments that would be, by today’s standards, considered immoral and illegal were conducted at no less than 30 universities across North America. Historians commonly describe the project as having been aimed to create a ‘Manchurian Candidate;’ a captured enemy brainwashed into infiltrating their own government.
MKUltra was a top-secret cold-war era program targeted at obtaining high-profile information and exploring the possibility of mental reprogramming on anyone considered to be a potential threat. Often, the first ‘candidates’ were actually unwitting citizens forced into participation (for an early and eye-opening documentary see this). Under the guise of procuring protection of US citizens from communist forces, the CIA initially administered LSD to those considered to be on the fringes of society – prostitutes, prisoners, patients with mental disorders and drug addicts – as they were thought to be the most susceptible to influence. Alongside these experiments, LSD and other psychedelic drugs were also given to doctors, CIA employees and those considered to be among the general public. Equally wrongful, the atrocities that happened in the dark realm of MKUltra were conducted at Universities by department authorities with no knowledge of the true purpose of the research. Indeed, some of the CIA funding was laundered through other sources directly connected with the institutions, while faculty PIs were completely in the dark as to the true motivation for the studies.
The research was at the time considered cutting-edge and remarkably some of it undertaken as having genuine potential for therapeutic benefit. The idea behind experimental therapies such ‘psychic driving’ and later, what was known as ‘depatterning therapy’, for example, was to take the mind of a patient and essentially wipe it clean through repeated sessions of LSD administration, electric shocks and lack of sleep. The aim was to make them forget the source of their illness and make their mind essentially a blank slate from which they could begin anew. They would then begin the ‘repatterning’ component, requiring them to listen to taped ‘therapeutic’ messages for hours, days, weeks and months upon end. Here’s one study, on patients with Schizophrenia conducted by Dr. Cameron involving depatterning. Evidently, these treatments seemed very promising. So why was the funding for LSD and other psychedelic experiments cut? Officially, it was because the effects of these drugs were found to be unpredictable, as stated by JS Earman, the CIA’s Inspector General at the time.
The effect of this illegal and immoral program of unwitting psychedelic drug administration was an incalculable science PR fallacy and an impetus for the backlash against LSD research that occurred in the late 60s and early 70s, making psychedelics research itself a true ‘acid casualty.’ Victims such as Velma Orlikow illustrate a typical example of consequences of the loosely constrained, paranoia-motivated program. She checked into Allen Memorial institute at McGill University in Montreal because of postnatal depression. Her long-term treatment under Dr. Donald Ewen Cameron included being administered LSD 14 times and then having listen exhaustively to repeated, taped conversations intended to be therapeutic. This torture was part of a developing technique called “psychic driving.” Orlikow did not recover. Rather, she spent the rest of her life suffering mental illness attributed to the therapy program. She is one of nine victims who in 1988 were given a portion of $750, 000 CAD by the Canadian Justice Department in an out-of-court settlement for the consequences of this type of manipulation.
Meanwhile, recreational LSD use was on the rise, becoming an important catalyst for and central part of the 6O’s counterculture movement. Baby boomers coming of age were exalting Timothy Leary towards an almost religious status. His Harvard academic cred symbolized the go-signal for “tuning in, turning on and dropping out”. Millions of Americans are reported to have consumed LSD. But where did this lead them? What enlightenment was achieved? How would society change? Well, it seemed the newly elected Nixon government wasn’t exactly the representation that the counterculture youth were hoping for, declaring “the war on drugs”. LSD became a Schedule 1 drug and the counterculture movement was left only with flashbacks to the better times from the past. Research on psychedelics as therapeutic agents on American and Canadian campuses came to a halt and the Stigma went from being a problem child to a full-fledged demon. Indeed, the sun had set on the ‘Age of Aquarius.’
The new realm of psychedelics research
The dust raised by what happened in the first twenty years of psychonautic exploration of hallucinogenic drugs appears to have settled. Research is now completely untethered to cold-war motivations and there is no ultra-secret program funding research to determine how to reach into the very core of the minds of individuals and assert complete control (interestingly, some labs have successfully turned to crowdfunding for financial support). Meta-research has identified important methodological shortcomings of the pioneering work, including the lack of basic control groups, follow-up measurements, substantial variation in dose and dosing, non-standardized criteria for therapeutic outcome and the use of fringe methods for determining outcomes of drug use, such as sensory isolation and sensory overload (Santos et al., 2016). Today’s studies with psychedelics are significantly more controlled and thereby safer. Participants remain under careful supervision in safe environments while undergoing the experience of psychedelics. Research dedicated towards a genuine exploration of psychedelics for therapeutic purposes and for basic understanding of brain function is currently underway and increasing. Centers specific to this research are now coming into existence, including the Multidisciplinary Association for Psychedelic Studies (MAPS), the Beckley Foundation and the Heffter Research Institute. Similarly, university labs primarily focused on psychedelic research are also more numerous.
But despite having over 50 years of research behind us, is there enough control and predictability tied to the use of these drugs? Can it be assured that in another 50 years we won’t look back on the current clinical trails to some degree, in the way we do of the early research? If that were the case, perhaps the current research would proceed without much attention. Instead, media coverage has reached respected realms including publications in Nature news, the New Yorker, New York Times and Nautilus. Moreover, LSD, Psylocibin and DMT are still Schedule 1 drugs and this fact still deserves all the careful consideration that it can employ.
A review published last month by Santos et al. covers much of the ground on which the last 25 years of work stands. It emphasizes six recent clinical trial studies involving LSD, Psylocibin and DMT. These six studies were singled out because they met the author’s criteria for being the most methodologically sound. Elgibility criteria included measures associated with peer-reviewed publication, structured diagnostics of anxiety, depressive or dependence disorders, placebo use, and validated scales for measuring changes in symptomology. Each study showed a reduction of symptoms associated with anxiety, depressive and dependence disorders. At a neurophysiological level, possible methods of action are discussed for each one.
The work sounds promising and shows much potential. This is cutting-edge research on the frontier of human knowledge regarding the brain and the mind – just as it has been since the late forties. Framed this way, it might be easier to understand the importance of keeping this research carefully controlled and not to dismiss what happened in the first 25 years as hysteria despite the change in political climate.
So what’s ‘the answer’? Part of it is likely to lie in improving the predictability of the effects on these drugs, especially LSD. In two of the previously mentioned reviews advocating the pharmacological use of psychedelics, hallucinogens remain described as largely “unpredictable” and “dependent on current psychological state and social environment.” This is the same consensus arrived at by the CIA in the 1960’s. Moreover, it’s a token anti-hallucinogen warning given on any standard drug abuse website, educational film, pamphlet or help line. Bad trips and flashbacks are simply not hysteria. Robin Carhart-Harris, head of Psychedelic research at Imperial College in London, acknowledges “…LSD has potential negative effects. Probably the crucial one is a bad trip. It’s not uncommon for people to have anxiety during a psychedelic drug experience…the experience can be nightmarish at times.” In regard to flashbacks, the phenomena is now officially termed: hallucinogen-persisting perception disorder and has been studied extensively.
The fact unpredictability remains the problem child of these drugs underscores the need for a more in-depth knowledge of their mechanism of action and long-term effects. It’s not as though there is no current insight into either of these and much progress has been made. For example many studies have shown the agonistic relationship between LSD and 5HT (serotonin) receptors and how this might promote some of the benefits observed. Carhart-Harris et al. published the first neuroimaging study of the LSD experience revealing it’s neural correlates – a landmark study that garnered much media attention. This study revealed vast changes in brain connectivity under the influence of LSD and makes important implications towards the neurobiological underpinnings of the LSD experience. In the past year alone his prolific lab has published no short of seven studies regarding the relationship between the experience of the drug and it’s effect on the brain. The most recent study (link) used this approach to investigate long-term changes in personality after an LSD use. These studies, investigating the more fundamental dynamics of psychedelic drugs go a long way towards reducing their unpredictability and thereby giving therapeutic research a much stronger foundation.
In conclusion, the new age of research is here and it’s growing, but perhaps a better understanding is needed on a more fundamental level before administering these drugs to patients with disorders. The risk of bad trips and flashbacks is still acknowledged, moreover the “unpredictability” factor still lurks like the ghosts of Timothy Leary and the MKUltra research program. Headway is being made in reducing it, but perhaps that could be a primary focus. Otherwise, as over the past 50 years, the research may only continue to proclaim it’s ‘potential’. Hopefully, in a time soon to come, we can see it’s use as standard.