Executive Summary – PSYCH: The Psychedelics As Medicine Report 3rd Edition

Psychedelics as medicine are at a crucial inflexion point. A growing number of studies are adding evidence to the astounding effectiveness of psychedelics to treat mental health and substance use disorders. Tireless work by daring researchers and relentless non-government organisations (NGOs) have made possible the renaissance of psychedelic research that we find ourselves in.

Exactly 50 years ago, most psychedelics were classified as controlled substances (Schedule I) under the Convention on Psychotropic Substances. The backlash against the ‘hippie’ culture also made it nearly impossible to study psychedelics, which showed initial successes in the treatment of alcoholism, anxiety, and other mental health disorders.

Forward-thinking investors and entrepreneurs now recognise the growing body of academic research. They, often with scientists advising them, are laying the groundwork for psychedelic-assisted therapy (PAT) at scale. As you will learn in this report, there are many areas where psychedelics are showing promise. Psychedelics are on course to become the next major paradigm shift. This blossoming industry marks the first significant innovation in mental healthcare since 1987 when antidepressants were first introduced.

This report examines six psychedelic substances in depth. These are: psilocybin (‘magic’ mushrooms), LSD, MDMA, ketamine, ayahuasca and ibogaine. The report includes sections dedicated to profiling each substance and identifying its legality around the world, as well as clinical trials or academic research underway to ascertain the potential benefits of these substances for treating a broad list of mental health conditions.

a Psilocybin

Psilocybin, the psychoactive substance (when metabolised as psilocin) in over 200 species of fungi, has shown promise, when combined with psychological support such as talk therapy, in the treatment of a variety of mental health disorders. Most research has been done to treat so-called treatment-resistant depression or TRD (depression that does not respond to conventional antidepressants – estimated to affect 77 million people worldwide). Two separate providers, COMPASS Pathways and the Usona Institute have received Breakthrough Therapy designation (BTD) from the US Food and Drug Administration (FDA) for synthetic versions of psilocybin for use as part of psychedelic-assisted psychotherapy for TRD and major depressive disorder (MDD), respectively. COMPASS Pathways recently finished its phase IIb trial and will publish results later in 2021. The FDA designation is a step closer to licensing approval for this therapy in the US, which may be granted as early as 2025.

b LSD

LSD has shown tremendous early potential in treating depression, anxiety, PTSD, attention deficit hyperactivity disorder (ADHD), and cluster headaches, among others. Although less intensely studied since the turn of the century, LSD has played a pivotal role in early research and even discovering serotonin (a neurotransmitter) in the brain. The practise of microdosing psychedelics (taking regular, sub-perceptual doses of a psychedelic, in fractional quantities not strong enough to result in hallucinations), which, anecdotally, is believed by many to enhance productivity and stimulate creativity, is beyond the scope of this report, due to a lack of scientific evidence proving its efficacy.

c MDMA

MDMA-assisted psychotherapy is showing incredible promise for the treatment of PTSD; so much so that it is expected to receive FDA approval by 2023, having received BTD in 2017. The therapy has been so effective that a phase III clinical trial conducted by the Multidisciplinary Association for Psychedelic Studies (MAPS) found that two-thirds of the study participants who completed a course of MDMA-assisted psychotherapy no longer met the criteria for a PTSD diagnosis. Earlier studies showed that these effects held for up to 12 months after treatment. MDMA could be treating patients within six months after approval in the US and Israel, with European Medicines Agency (EMA) approval following a phase III trial in Europe.

d Ketamine

Ketamine is the only psychedelic profiled in this report that features on the World Health Organisation (WHO) List of Essential Medicines. Ketamine is widely available as a general anaesthetic. It can also be used ‘off-label’ (for purposes other than anaesthesia, which have not been approved) to treat conditions as varied as depression, anxiety, suicide ideation (SI), chronic pain and fibromyalgia. It is currently available in clinics throughout the US for these purposes and is starting to be offered in Europe. Ketamine clinics may prove to be a successful prototype for other psychedelic-assisted therapies for patients once approval has been granted to psilocybin or MDMA, for example. Esketamine, one half of the ketamine molecule, is the primary ingredient in a nasal spray patented by Johnson & Johnson under the name Spravato – the only FDA and EMA approved psychedelic medicine for the treatment of TRD.

e Ibogaine

Ibogaine, which originates from West Africa, has been used for decades to treat substance use disorders (SUDs) in countries such as Mexico. It has shown efficacy in reducing a patient’s misuse of stimulants, opiates and alcohol, and reducing symptoms of withdrawal (from opiates) after administering a single dose. Several ‘second generation’ (novel compounds based on existing psychedelics) psychedelics are being developed to harness the anti-addictive effect of ibogaine without the relatively high health risks, specifically heart rhythm disturbances, associated with the substance.

f Ayahuasca

Ayahuasca, which has been in use for millennia, is a psychoactive brew that combines several ingredients, DMT and MAOIs, that one consumes as tea. Although less well studied in clinical trials, the mixture and the isolated psychedelic DMT show promise in treating depression, anxiety, eating disorders, and could even help those with strokes to recover better. Many have sought ayahuasca experiences through partaking in ayahuasca retreats – particularly common across South and Central America.

Other psychedelics also show promise in the treatment of mental health and substance use disorders. These include Salvia Divinorum, mescaline (from the peyote cactus), DMT, 5-MeO-DMT, kratom, 2C-X, nitrous oxide and novel compounds (also called ‘second generation’ psychedelics). The future approval of the major psychedelics will probably clear a path for further clinical research and development of these other psychedelics into medicines.

There is significant support among sections of society to allow researchers to examine the potential benefits of psychedelics. PSYCH & Blossom’s proprietary consumer data shows that 69% of adults in the US, the UK, Canada, France and Germany would consider psychedelic-assisted therapy. Two-thirds support the legalisation of psychedelics for research purposes. Six out of ten participants from a representative sample in each country (3,050 respondents total) were curious to learn more about psychedelics as medicines.