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Hallucinogens and depression | Psychology today

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<p> Hallucinogens, or "psychedelics," are substances that induce a "non-ordinary" experience of consciousness. Used for thousands of years (at least), the medical potential for powerful psychotropic substances has come in and out of fashion. </p>
<p> Mescaline was isolated in 1897 and used in experiments as a truth serum and for the treatment of psychiatric disorders. just after the second world war. LSD was made available to scientists free of charge by the pharmaceutical company Sandoz and widely used in medical research in the 1950s and 1960s, with tens of thousands of patients (and researchers) to try schizophrenia and addiction. l & # 39; alcohol. LSD has also been used in psychotherapy to "help" patients recover from their neuroses, for patients with severe pain, and in an experiment with theology students where it has been found to induce mystical experiences. Albert Hoffman published the synthesis of psilocybin in 1959 and has also been studied for various conditions. Surprisingly, few concerns have been raised about the safety of these hallucinogens in these early articles </p>
<p>. In 1966, the United States banned LSD at a time when medical science applied a much greater methodological rigor. Most psychedelic research was almost worthless by the new standards, being mainly thousands of case studies without controls and without objective measures of symptoms (such as symptom rating scales). Researchers in the mid-1960s using more modern research techniques and longer follow-up have not been able to replicate the luminous results of the past. With the illegal psychedelics, research has become much more difficult and enthusiasm for their treatment potential has diminished. Of the major modern hallucinogens (psilocybin, mescaline, DMT, ketamine and MDMA), only ketamine is still legal and generally used as anesthetic. </p>
<p> In current medical practice, especially in psychiatry, hallucinogens are considered potentially dangerous. ongoing psychotic disorders, especially for people with a personal or family history of schizophrenia and bipolar disorder, and should be avoided. It would be a professional mistake (not to say illegal) for a doctor to administer LSD to a schizophrenic patient today. However, the lack of success of almost all therapies, medical or otherwise, for treatment-resistant depression and some substance abuse disorders led researchers to reconsider hallucinogens, starting with ketamine. </p>
<p> All these agents act on a particular serotonin receptor, 5HT-2A, and ketamine is furthermore an NMDA receptor antagonist. The activation of this serotonin receptor seems to influence "existential concepts of self, including moral values, self-identity and purpose". This illuminates the atmosphere and makes people feel motivated to change. Interestingly, modern studies of ketamine for depression focus on a low dose (typically 0.5 mg / kg for 40 minutes in an IV, while 1 to 4 mg / kg are typically used for anesthesia ) and the hallucinogenic properties of ketamine are minimized. dose. However, some studies have shown that the amount of dissociation symptoms measured during the infusion was consistent with a longer antidepressant effect. All ketamine studies tend to be rather small, and some show no correlation between hallucinogenic effect and antidepressant effects. </p>
<p> The other hallucinogen with a promising modern research is psilocybin, derived from fungi. There are also a number of small studies on alcohol and tobacco addiction, anxiety and depression at the end of life, obsessive-compulsive disorder and treatment-resistant depression. London scientists have used fMRI to look for brain mechanisms in their study of psilocybin and depression. 19 patients received psilocybin, and all 19 saw their depression scores drop significantly (in fact, on average, the depression scores were halved) one week after the dose. 47% still met treatment response criteria 5 weeks after dosing. </p>
<p> The fMRIs were also interesting, showing a decrease in blood flow to the amygdala (the center of the "fear" of the brain) correlated with antidepressant effects. FMRI can measure the overall "connectivity" of the brain, or how much communication is going on between different parts. <em> The increased connectivity </em> of some parts of the prefrontal cortex and parietal lobe predicted a therapeutic response at 5 weeks, just as <em> decreased connectivity </em> between parahippocampal cortex and prefrontal. </p>
<p> In all of these modern studies, carefully conducted under controlled conditions with medical and psychological support, psychedelics appear to immediately reduce depressive symptoms and also promote positive changes. The side effects of ketamine include changes in vital signs, and some people who take ketamine and psilocybin experience painful hallucinations and do not like feelings of dissociation (others seem to like that feeling ). Since the only other end-of-line treatment that works very quickly for depression and, especially, acute suicidality, is electroshock therapy, the risks and benefits of psychedelics in this context is a different conversation (currently experimental) than for standard outpatient treatment. . It seems likely, unless larger studies take a surprising turn, that ketamine, in particular, is more widely used in general practice, particularly in closely monitored settings such as internal psychiatric units and wardens. emergency. This is not the optimism of a 1950s researcher who likes to do LSD with his patients … it's science </p>
<p> The main disadvantage of these agents is that they do not seem to work very long in some people. but we may need to determine the mechanisms, the dosage, and how to space the re-treatments if necessary. As their study expands, we will likely find more cases of induced psychosis or mania and learn more about patients to completely avoid hallucinogens. </p>
<p> In the meantime … I highly recommend <strong> do not try this at home </strong>. Every doctor and emergency psychiatrist of the country can tell you a horror story of something terrible after the use of hallucinogens, death following instability of vital signs (hyperthermia ) after using synthetic MDMA to one of my patients became psychotic for 8 months straight (through 6 hospitalizations!) after a few days of using fungi. Any agent with potent effects may also have potent side effects, and should be used with knowledge of risks and benefits and appropriate care. </p>
<p> copyright Emily Deans MD </p>
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