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Most of us will have grown up holding the view that all drugs are ‘bad’ for us, but is this so? Might it be that some types of psychedelic drugs could help us to better manage or even heal our mental health problems, particularly when used in combination with psychotherapy? The author of this perspective piece from the journal Frontiers in Pharmacology, Dr. Eduardo Schenberg, Brazilian Neuroscientist and Honorary Researcher at Imperial College London UK, gives us a rundown of the evidence to answer this question.
Schenberg says that psychiatry is in crisis because it does a lot less research looking into new types of substances that can be used as medications for people with mental health problems compared to what it used to. Approval of new drugs has fallen sharply since the 1990s according to the US Food and Drugs Administration (FDA), which is one of the main international bodies that certify use of medicines.
Schenberg also explains that views in some quarters of psychiatry have evolved, leading to changes in how mental health problems are now understood and treated. Specifically, some researchers have broken away from traditional thinking about psychiatric diagnosis, which uses ‘disorder’ labels based on clusters of symptoms, because there has been a long-standing debate about whether they are scientifically sound. The move is instead towards more granular but also linked-up neuroscientific explanations about our genetics, molecules, cells, brain circuitry, behaviour, physiology, and individual views about our experiences. It explains how we sit on a ‘normal’ continuum (i.e., a sliding scale) of severity, rather than ‘having a disorder’ or ‘not’. Schenberg says this change invites us to think about drug development in a new way, with a particular focus on the role of using psychedelics in combination with psychotherapy.
A range of psychedelic substances have been tested in different studies but not necessarily in combination with psychotherapy, including:
• 2-(2-Chlorophenyl)-2-(methylamino)Cyclohexanone (ketamine)
• 3,4-MethylenodioxyMetamphetamine (MDMA), which should not be confused with the street drug “ecstasy” (also known as “molly”), which often does not contain MDMA but rather a mix of other substances.
• Naturally occurring alkaloids, including 4-phosphoriloxy-N,N-dimethyltryptamine (psilocybin, which is present in hundreds of Psilocybe ‘magic’ mushroom species)
• Lysergic Acid Diethylamide (LSD), and
• 12-Methoxyibogamine (ibogaine, from the Tabernanthe(eee) iboga – a rainforest shrub native to Central Africa.
All can be taken orally but work in quite different ways in terms of how they affect the brain – see the original paper below for more details.
At the time of publishing the article in 2018, Schenberg explains that ketamine is the most studied substance, having been used as an anaesthetic for several decades. It has been tested in several Phase 2 and a few Phase 3 Randomised Controlled Clinical trials (RCTs) (i.e. a trial that compares groups of treatments to see if they work – see our glossary for more information about what this is – where phase 2 means tested mostly against usual treatments or nothing at all while phase 3 against best available standard treatments) – mostly for people with depression. However, ketamine also shows promising results in for people with obsessive-compulsive disorder, post-traumatic stress disorder (or PTSD), suicide, and alcohol and cocaine use disorders. Nine ‘Systematic reviews with meta-analyses’ (i.e. a summary of lots of individual studies/trials – again if you’re not sure what this means, check out our glossary) of clinical trials show few incidents of harm and short-term improvement in positive outcomes for most people.
MDMA is the second most researched psychedelic in clinical studies. It has been tested in seventeen phase 2 RCTs, with impressive results particularly in PTSD, but also social anxiety in adults with Autism, existential anxiety (i.e., so angst about big issues, such as life’s meaning), and alcohol use disorder, where again serious incidents of harm were rare.
Psilocybin comes in third. It has a very high safety record or ‘ratio’ and low risk when taken unsupervised according to eight trials for major depression, cigarette, alcohol, and cocaine use disorders, and existential anxiety about life-threatening diseases, including mostly cancer.
LSD, the most potent psychedelic used in clinical trials, has a very high safety record with long lasting effects and is unrelated to major health problems after unsupervised use. That said, it has only been looked at in two Phase 2 trials for people with existential anxiety who were terminally ill, where Schenberg the lack of research for this substance is because of stigma from large-scale recreational use since the 1960s. However, many previous studies show promising results, which led to psychedelic-assisted psychotherapy in the 1970s and treatments offering repeated low doses to improve psychoanalysis in recent years. In 2012 a systematic review with meta-analysis including studies over the last sixty years showed that LSD has potential for treating alcohol use disorders.
Lastly, ibogaine has not yet been tested in clinical trials, and efforts to develop this treatment for people with opioid (i.e., heroin or fentanyl) addiction fizzled out in the 1990s. Compared with other psychedelics, there are important safety concerns about this drug, including heart problems. However, Schenberg makes the point that the seriousness of this type of addiction problem should encourage researchers to test the safety of the drug properly given the promising results with opioid and psychostimulant addiction so far.
Schenberg also outlines why Psychedelic-Assisted-Psychotherapy (or PAP) may be useful going forwards:
Although, there are drug free sessions before and after receiving psychedelics in PAP, psychedelics are only dispensed in a few sessions. Trials show Ketamine has large positive improvements after one to twelve sessions, MDMA three, psilocybin and LSD two, while ibogaine may be effective after just a single session, even for patients that are considered “treatment resistant”, which is much faster than current treatments. This is important because most psychiatric drugs tend to be offered daily for much longer periods of time, which makes it harder to disentangle if it was the drug that changed the person’s experience over time or something else. It also reduces the problem of people not taking their medications as prescribed, but also the risk of toxicity, side-effects, abuse and addiction, and withdrawal symptoms from taking them, where often greater harm is caused by long-term use.
During the sessions, the person is monitored by health professionals, listening to instrumental and evocative music, often using eyeshades to look inwardly and be open to feelings, thoughts, and memories, and are free to engage in psychotherapy at any time. Some trials have used more non-directive transpersonal, or manual based addiction or cognitive behavioural psychotherapies.
PAP is viewed as a temporary induction that can result in processing of a person’s deeply meaningful experiences with positive long-term mental health consequences, differing from the traditional psychiatric view of a person needing daily ‘corrections’ in ‘brain dysfunction’. For this reason, there remains a question about whether developing new drugs based on these substances without the psychedelic effects will be equally as effective? The data so far shows they are not.
The fact that these five different substances work differently biologically but still improves a range of mental health conditions also encourages us to think more about whether diagnostic categories are so helpful – if the biological mechanisms of the drugs are different but the results are the same across conditions, then do diagnoses matter? By evoking deeply meaningful past memories and other individual experiences in non-ordinary states of consciousness with psychedelics, PAP can also potentially uncover the most relevant material to work on in psychotherapy.
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