The medical properties of psychedelics have their roots in the traditions and rituals of indigenous cultures and have been used for hundreds of years.
From a Western medicine perspective, research points to the potential therapeutic benefit of these substances to help alleviate mental health-related conditions and the ability to improve psychological well-being.
As our medical knowledge of psychedelic substances increases owing to advances in neuroscience and psychopharmacology, researchers are gaining a greater understanding of how they work in the brain.
They are known to promote brain plasticity in a similar way that current antidepressants do, the effects of which are associated with changes in both the brain-derived neurotrophic factor (BDNF) and local serotonin levels.1,2
In fact, psychedelics target the specific serotonin receptors in the brain to generate the subjective effects associated with these substances.1 As serotonin receptors play an essential role in mood and psychotic disorders, psychedelics can potentially provide treatment strategies for mental health-related conditions.
Investigation of the therapeutic properties of psychedelics shows potential benefits for the improvement of several conditions, including those related to substance abuse, anxiety, depression and bipolar syndrome, as well as eating and personality disorders.4–6
Research already shows that these substances improve the symptoms of many psychological conditions and can also treat them.
It’s important to note that the effects of psychedelics are not limited to their therapeutic potential. Studies in healthy subjects indicate improvements in cognitive and emotional functions, psychological well-being and quality of life.7–9
Interestingly, the results that Western medicine is recording from this research correlate with the properties attributed by those indigenous cultures that have used them for centuries.
The potential therapeutic effects associated with psychedelics are usually reinforced when either adequate spiritual guidance (in the case of indigenous cultures) or psychotherapy (in Western medicine) is provided with the psychedelic experience.10,11
The subjective effects
Psychedelics can induce powerful introspective experiences that significantly impact users’ perceptions of their lives and problems. Subjects often refer to
- ego dissolution
- a higher consciousness of important things
- improved ability to understand others
- greater acceptance of oneself and life events
- and other similar processes related to personal growth.8
These experiences can be joyful … but they can also be overwhelming and sometimes hard to experience, process and understand.
Although negative experiences cannot be predicted, using psychedelics in an appropriate environment — with the proper preparation and guidance — can reduce the risk of bad ones. This is usually referred to as the “set and setting” and is typically controlled by a guide, which can be a shaman, a psychotherapist or a combination of both.
The role of the guide is to prepare the user for the experience, to be present and to help with interpretation once the session is finished — so that patients can fully understand what has happened.
To follow safety measures, guides are often accompanied by medical staff such as psychiatrists and nurses, which is an essential requirement in many clinical practices.
Routes of administration
The route of administration will depend on its availability and the type of effect or outcome desired. Dosage forms usually include oral (psilocybin and 3,4-methylenedioxymethamphetamine [MDMA]), inhaled (N,N-dimethyltryptamine [DMT]) and nasal (ketamine). In clinical settings, however, intravenous and intramuscular administration are also used.
Oral administration often has slow-acting and long-lasting psychedelic effects, which gives the user a more extended experience with more opportunity to process, learn and integrate the experience while it’s happening.
This is typically the case with Ayahuasca rituals or psilocybin/MDMA-assisted therapy. Depending on the substance and dose, psychedelic experiences usually last 3–12 hours.
Nasal, inhaled or injected routes of administration usually have fast-acting and short-lasting effects, sometimes with intense experiences during which the user has fewer chances to process, learn and integrate the experience while it’s happening.
This is typically the case with smoked 5-MeO-DMT rituals, Salvia divinorum or ketamine assisted-therapy. Depending on the substance and dose, psychedelic experiences usually last 5 minutes to one hour.
Contemporary routes of administration for psychedelics are almost the same as those used by indigenous cultures. Clinical practice and research already offer some alternatives, but new options are still to be explored and vaporisers might become more common.
Clinical trials
Globally, there are approximately 70 clinical trials currently testing psychedelics for specific medical conditions. More than 50% of these studies involve MDMA and psilocybin for depression and post-traumatic stress disorders.
Others include LSD, Ayahuasca, salvinorin A and other plants/molecules to treat substance abuse, mood and anxiety disorders.
Only three clinical trials are at Phase III and only esketamine (structurally similar to ketamine) has been approved for medical use (since 2019 in patients with treatment-resistant depression).
It is important to note that ketamine was approved as an anaesthetic during the 1970s and it has been used off-label to treat mood disorders for several decades.
Other compounds, such as MDMA and psilocybin, are allowed in expanded access or compassionate use in countries including the US, Canada, Israel and Switzerland. Furthermore, on 1 July 2023, Australia will be the first country to approve the use of MDMA and psylocibin for medical purposes.
Medical use and practice
Ketamine is already used to treat major depression, MDMA is about to be approved for post-traumatic stress disorder (PTSD) and psilocybin and other psychedelic drugs are already quite advanced in clinical trials.
It is just a matter of time before these drugs are approved for several mental health-related conditions. It should be expected that the medical use of these drugs will be highly regulated, like benzodiazepines or opioids, as they are controlled substances.
Once approved, regulation will determine whether these drugs are available via public health systems, if private health insurance companies will cover the treatments and whether they must be consumed in a controlled environment or if patients can take them at home.
The requirements for these controlled environments will probably be highly regulated.
It currently looks likely that there will be two main approaches. The first relates to typical clinical sites or hospitals in which patients are treated in a clinical environment — a combination of a department in a psychiatric hospital and a psychology practice.
These sites might need the capacity for patients to stay for a period of time to be treated for several days.
The other option is welfare sites with medical licenses, which would combine a well-being centre and a clinical trials environment. These would be clinically regulated establishments wherein patients can be treated in a less clinical setting … but probably under the same regulatory framework.
Current ketamine clinics are already a mix of these two approaches. Although extant sites are not regulated because the area of psychedelic treatment is still extremely new, they usually operate under the same regulations as private clinics.
Conclusion
Given the interest, investment and number of clinical trials in progress, the indication is that psychedelic substances will radically change the treatment options for people with severe mental health disorders in the coming years.
As with all new areas of medicine, it is essential that governments act quickly to put appropriate regulations in place to protect the public and allow the sector to progress in a way that encourages investment, research and new drug development.
Accelerating the establishment of this exciting new area of neurosciences and psychopharmacology has the potential to improve the quality of life for millions of mental health sufferers.
References
- A.C. Kwan, et al., “The Neural Basis of Psychedelic Action,” Nature Neuroscience 25(11), 1407–1419 (2022).
- R. Moliner, et al., “Psychedelics Promote Plasticity by Directly Binding to BDNF Receptor TrkB,” Nature Neuroscience 26(6), 1032–1041 (2023).
- S.M. Thompson, “Plasticity of Synapses and Reward Circuit Function in the Genesis and Treatment of Depression,” Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 48(1), 90–103 (2023).
- N. Ledwos, et al., “Therapeutic Uses of Psychedelics for Eating Disorders and Body Dysmorphic Disorder,” Journal of Psychopharmacology (Oxford, UK) 37(1), 3–13 (2023).
- B.L. Roth and R.H. Gumpper, “Psychedelics as Transformative Therapeutics,” American Journal of Psychiatry 180(5), 340–347 (2023).
- M.M. Urban, et al., “Mini-Review: The Neurobiology of Treating Substance Use Disorders with Classical Psychedelics,” Frontiers in Neuroscience 17, 1156319 (2023).
- D.F. Jiménez-Garrido, et al., “Effects of Ayahuasca on Mental Health and Quality of Life in Naïve Users: A Longitudinal and Cross-Sectional Study Combination,” Scientific Reports 10(1), 4075 (2020).
- P. Orłowski, et al., “Naturalistic Use of Psychedelics is Related to Emotional Reactivity and Self-Consciousness: The Mediating Role of Ego-Dissolution and Mystical Experiences,” Journal of Psychopharmacology (Oxford, UK) 36(8), 987–1000 (2022).
- P.J. Teixeira, et al., “Psychedelics and Health Behaviour Change,” Journal of Psychopharmacology (Oxford, UK) 36(1), 12–19 (2022).
- M. Cavarra, et al., “Psychedelic-Assisted Psychotherapy — A Systematic Review of Associated Psychological Interventions," Frontiers in Psychology 13 (2022): www.frontiersin.org/articles/10.3389/fpsyg.2022.887255.
- E.E. Schenberg, "Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development," Frontiers in Pharmacology 9 (2018): www.frontiersin.org/articles/10.3389/fphar.2018.00733.
