Psychedelic-Assisted Psychotherapy for Post-Traumatic Stress Disorder, Anxiety Disorders, Mood Disorders, or Substance Use Disorders

Hallucinogens include many different drugs, which are often called “psychedelic” drugs. The US National Institute on Drug Abuse categorizes these drugs into 2 categories: classic hallucinogens and dissociative drugs. Both types of psychedelics can lead to hallucinations - sensations and images that seem real although they are imaginary. In addition, an individual using dissociative drugs can feel out of control or disconnected from their body and environment. Classic serotonergic psychedelics act primarily by a complete or partial agonist action on brain serotonin 5-hydroxytryptamine 2A receptors. Examples of classic psychedelics are LSD, mescaline, psilocybin, and ayahuasca (also identified as N,N- dimethyltryptamine [DMT]). Examples of dissociative drugs are phencyclidine, ketamine, dextromethorphan, and Salvia (Salvia divinorum). Psychedelics were tested for clinical use prior to the 1960s. However, methodological issues in clinical trials and political concerns have prevented the use of psychedelics in mainstream medicine. In 2010, it was reported that psychedelics were used by more than 30 million consumers in the US. Clinically, researchers acknowledge psychedelics as a potential effective drug for mental health conditions. Researchers and clinicians are testing the clinical effectiveness of psychedelics for mental illness treatment due to the improvement in research methods that reduce ethical and methodological concerns toward psychedelic trials. The wider application of psychedelics has also been motivated by a perceived lack of innovation in mental illness treatment. The number of new molecular entities for psychiatric conditions approved by the US FDA decreased from 13 in 1996 to 1 in 2016. One example of the psychedelics adopted for treatment is ketamine (not used in combination with psychotherapies) that has been used for the treatment of depression and post-traumatic stress disorder (PTSD), as reviewed in 2 CADTH reports. Other psychedelics, such as psilocybin and ayahuasca are increasingly being tested for their efficacy in treating mental illnesses. In addition to their use as stand-alone agents, psychedelics can be used in combination with psychotherapy (i.e., psychedelic-assisted psychotherapy). There are a wide variety of psychotherapies that may be used for the treatment of mental health conditions, including guided support that helps patients focus inward on their thoughts and better facilitate participant introspection and cognitive behavioural therapy (CBT) that combines different types of cognitive therapy and behavioural therapy. Psychedelic-assisted psychotherapy is often led by licensed professionals with training in administering psychedelics and monitoring their use. Psychedelics may work by altering a patient’s consciousness. They may also affect a patient’s subjective perspectives and approaches to processing thoughts, emotions, and behaviours, thereby providing an alternative therapeutic experience to psychotherapy alone. While psychedelic-assisted psychotherapy has been recently tried in patients with anxiety, depression, substance use disorder, and PTSD, some researchers consider the treatment response to be unsatisfactory in patients with mood disorder. This report aims to summarize the clinical effectiveness and safety of psychedelic drug-assisted psychotherapy for PTSD, anxiety disorders, mood disorders, or substance use disorders, in addition to clinical guidelines for the use of psychedelic drug-assisted psychotherapy.