A real therapeutic option?

About one third of people affected by depression experience no improvement under established pharmacological and psychotherapeutic treatments. This increases the pressure to explore new therapies. Currently, psychoactive substances as medications are again coming into focus. They may not only work in depression, but caution is required.

These substances are known from their recreational use, since they alter consciousness and thus perception: psilocybin and lysergic acid diethylamide (LSD), or also 3,4-methylenedioxymethamphetamine (MDMA). But that does not exclude the possibility that under strictly defined conditions they might also have therapeutic effects. History in fact shows that substances have sometimes been assigned rather arbitrarily to the group of medications or to that of drugs, and this classification has often shifted.

Physicians such as Dr. Tomislav Majic of the Psychiatric University Clinic at Charité say that, through the altered state of consciousness these substances induce, new insights can be gained in a medical-therapeutic context: people can better perceive what they actually feel, they may attune more strongly to the thoughts and feelings of others, and their social connectedness may improve.

In the »Deutsches Ärzteblatt«, the psychiatrist writes that the strongest evidence currently exists for the treatment of depression with psychedelics, especially psilocybin, as well as for the treatment of post-traumatic stress disorder (PTSD) with MDMA. The positive effects of therapy often last for weeks and months, he notes.

Dosage and treatment intervals differ fundamentally from conventional psychiatric medications. Psychoactive substances are administered only a few times. Whether the treatment succeeds depends greatly on the experiences the person has under the substance and on how well they are therapeutically guided.

During therapy, it is also possible that a present therapist suggests things to the patient, who is especially receptive due to the altered state of consciousness, but which may not necessarily be helpful. There is a danger of boundary violations by therapists. Patients give up a certain degree of self-determination to the therapists.

This is not the only known risk. Majic lists complications such as psychotic reactions, persistent perception disorders (mainly visual), anxiety disorders, as well as depersonalization and derealization syndromes. In addition, new disorders can develop based on the experiences. Nevertheless, large studies confirm the positive effects.

To harness the potential of psychoactive substances while minimizing risks, more sophisticated study designs are needed. Unlike other medications that can be tested well against placebo in double-blind trials, participants clearly feel the effects of the active drug, and thus know they did not receive a placebo – and the therapists know as well. This can significantly distort results.

The expectations of the physicians also play an important role in these studies, because the way they express themselves influences the patients. Moreover, according to Dr. Mattgias Knop, senior physician at the Max Planck Institute of Psychiatry in Munich, writing in the Deutsches Ärzteblatt, researchers’ expectations of a positive effect may also influence how they interpret the results.

Before consciousness-altering substances can actually be approved for depression, anxiety disorders, or PTSD, major hurdles must be cleared in research, regulation, and law. In Canada, Australia, and Switzerland, psilocybin may be used against depression in exceptional cases. In Australia, MDMA is approved for post-traumatic stress disorder (PTSD). Worldwide, however, regulation differs: in some places psychedelics are strictly controlled, while in others possession of small amounts is legal. In the Netherlands, on July 1 of this year, an important legal amendment came into force: in the »Act on New Psychoactive Substances«, the Dutch government imposed a comprehensive ban on so-called designer drugs, including all known MDMA analogs such as 6-APB, MDA, and methylone.

The reason is rampant consumption, the production of these drugs in the Netherlands, and their global distribution from there. The law also has consequences for therapists who had previously offered »trip therapy«, which people from other countries sought out in the Netherlands for a fee. Such therapy is still possible if psilocybin is used.