Psychedelic psychotherapy is the controlled medical use of psychedelic substances such as LSD, Psilocybin and MDMA to treat serious psychological disorders such as treatment-resistant depression or Post Traumatic Stress Disorder, addiction syndromes and end-of-life anxiety(1, 2).
As a psychiatric application Psychedelics appear to function differently to other drug-based treatments. While there is some change directly made to the serotonin system and brain areas such as the thalymus or anterior cingulate cortex (both involved in the processing negative emotion)(3,4) the most profound effects of therapy seem to result from the subjective experience the subject has with relation to their own introspection and self-assessment. The experience gives the subject a space within which they are able to understand their affliction/behaviour from a new perspective and gain an understanding not previously available. This seems to lead to long-lasting changes in the subject’s behaviour or lifestyle and in turn their mental health(5).
Screening and support is incredibly important when it comes to psychedelic therapy. One can become confused and agitated in losing their sense of self or being confronted by their current situation in life with the apparent clarity found in the experiences. There have, to date, been no clinically adverse reactions in subjects chosen for trials with psilocybin, MDMA Ketamine or LSD. This is due to the diligent screening processes and active psychotherapy which is consistent for some time prior to, during and after the drug sessions. Below are brief overviews of how, and which, psychedelics are currently being explored for psychotherapeutic applications.
Psilocybin (4-phosphoryl-hydroxy-N,N dimethyltryptamine)
Psilocybin is a simple chemical found in ‘magic mushrooms’. As the primary psychoactive component of the ‘magic mushrooms’, Psilocybin has been used for millennia in rituals and ceremonies throughout Mexico. There is also evidence of use among Nordic cultures in ancient Northern Europe – Vikings.
Psilocybin has been given Breakthrough Therapy designation by the U.S FDA for its potential use in mental health treatment. Psilocybin has been used in multiple trials over the last 20 years with great success in small subject groups. The conditions that psilocybin has potential to treat include end-of-life anxiety, nicotine addiction, cocaine addiction, treatment-resistant depression and eating disorders.
It has also been used to reliably induce what are known as ‘mystical’ experiences – more commonly known as ‘religious’ experiences – in trial subjects. Psilocybin has recently been effectively decriminalised in Denver, Colorado and Oakland, California. However, it is important to note that Psilocybin is categorised as a Class A drug in New Zealand along with methamphetamine and heroin. It’s use, even as a medicine, is illegal.
Psilocybin has relatively low toxicity with an LD-50 in rats of 280mg/kg. To put this in perspective an active dose for Psilocybin is in the 35-80mg range generally and a potentially lethal dose for an 80kg person would be 22,400mg. Although we are not quite sure how one would administer such a dose there are many psychological risks with psilocybin use. Subjects in trials are carefully screened for psychological sensitivities or pre-conditions which may indicate that the powerful, often life-changing psilocybin experience may not be safe. To read more thoroughly on specific applications and trial results for Psilocybin please click here
MDMA (3,4 methylene-dioxy-methamphetamine)
MDMA is a psychedelic amphetamine related to Mescaline found in the Peyote and San Pedro cacti. It has non-hallucinogenic effects primarily increasing empathy and inducing euphoria in the user. It is part of a circumscription known Empathogens. MDMA was originally used in psychotherapy primarily as an adjunct to couple therapy or marriage counselling and for general emotional and spiritual development with great success.
Initially the rogue pharmacist Alexander Shulgin introduced therapist Leo Zeff to MDMA. As Zeff had previously had great success using LSD in his practice before it was made illegal, MDMA was of great interest and eventually became an integral part of his on-going practice and training methods. MDMA is currently the most well-researched of the psychedelics with regard to specific psychiatric application.
For over 10 years dedicated workers Annie and Michael Mithoefer have been conducting trials in conjunction with the Multidisciplinary Association for Psychedelic Studies using MDMA to ameliorate treatment-resistant PTSD in combat veterans and sexual abuse survivors in the U.S.A, Canada and Israel. To date, these trials have had success rates above 80% of patients no longer meeting the criteria for PTSD. These trials have now moved to Phase-III multi-site trials with a view to have MDMA re-classfied as a prescribable medicine in the U.S.A by 2022. For a more thorough overview of this work and the earlier work in the 1970s and 80s, please see here and here.
LSD (Lysergic acid diethylamide)
LSD – more commonly known as Acid was first synthesized in the 1930s by Albert Hoffman of Sandoz Laboratories in Switzerland in an effort to create drugs to stem bleeding during childbirth. After an apparently accidental ingestion Hofmann became somewhat of an evangelist for the psychotherapeutic potential of the drug. Since then it has gone through many stages of reputation.
Initially, it was a promising drug which therapists used as a ‘psychotomimetic’ assuming it imitated various psychoses and schizophrenia-type conditions with a hope of understanding their patients better. It was then used very successfully in early therapy treating mild mood disorders and alcoholism. There is some current enthusiasm to use LSD in trials to treat addictions and treatment-resistant depression (see here).
LSD has also gained huge popularity as a drug to ‘micro-dose’ due to it being easy to dose accurately and store for long periods. The anecdotal consensus is that LSD micro-doses have a generally positive effect on mood and productivity but there is a a big question mark over these anecdotes due to the placebo effect. A small number of limited studies have shown no negative effect and potentially some small positive effects from micro-dosing in a clinical setting.
Auckland University is about to start a micro-dosing trial with LSD as a prescription medicine taken ‘in the wild’. This will be a world-first study and will be invaluable to the understanding of micro-dosing effects in everyday life.
Ketamine
Ketamine has recently been used successfully in multiple trials as an intervention method treating intractable depression and thoughts of self-harm. Ketamine appears to induce neural plasticity (by inducing ‘long-term potentiation’) and neurotigenesis which may explain how it has it’s anti-depressant effect. It has an almost immediate effect alleviating depression symptoms within 24 hours. However, it has been shown to only be effective short-term as benefits tend to taper off in the 1-2 week range without integration support. This may be extended with psycho-therapeutic integration support, taking advantage of the short-term neural plasticity. Further research is needed to elucidate this.
Ketamine is currently legal as a therapeutic agent in New Zealand. However, access is very limited as therapists trained to use it are a vanishingly small group. We at Entheos hope to change that fact and make Ketamine a more widely available treatment with therapists trained in its use.
There is currently one FDA-approve Ketamine-based treatment in the form of a nasal spray called esketamine in the USA. This now also has approval from the US Veterans Association.
Mescaline (3,4,5-trimethoxy-phenethylamine)
With a history going back more than 6000 years, Mescaline was introduced to the Western world through the rituals of the Huichol and Chauvin people of Northern Mexico and the high Andes, respectively. First isolated from Peyote cactus by Arthur Heffter in 1897, mescaline became something of a sensation among psychologists. Through early accounts by Havelock Ellis, S. Weir Mitchell and peaking with 2 essays by Aldous Huxley, the transcendent nature of the mescaline experience exploded into academic circles.
In 1913, Knauer and Maloney carried out the first proper trial using mescaline in New York City. They were aiming to assess the ability of mescaline to induce a pseudo-schizophrenic state which could be exploited to better understand genuine schizophrenia. Once Merck Corporation made mescaline available to therapists in 1919, work began to explore that hypothesis. It was essentially a total failure and enthusiasm waned by the 1940s(though, the theory has been explored as recently as 1992).
With the advent of LSD in 1946 and subsequent furor in the psychiatric world, mescaline was left behind – until 1953. The British writer and academic Aldous Huxley was provided mescaline by a British-Canadian therapist friend, Humphrey Osmond. After his experience he penned the two papers The Doors Of Perception and Heaven And Hell. These two works reignited interest in both mescaline and psychedelics in general with a renewed hypothesis: could hallucinogens induce the ‘mystical’ experience recounted by sages, mystics, sadhus and messiahs for time immemorial? Recent research has gone a long way to supporting that notion. Mescaline enjoyed some clinical resurgence in the 1960’s but with the Nixon-area declaration of a war on drugs psychedelic research was almost entirely halted in 1970.
There are current trials planned or in progress utilizing mescaline.