The psychedelic renaissance is expanding our understanding of one of the most captivating scientific puzzles: human consciousness. Numerous research fields reveal new insights into how psychedelics affect the brain. Psychedelics are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. In recent years, scientific interest in serotonergic psychedelics (e.g., psilocybin and LSD) has dramatically increased. Clinical studies administering psychedelics with psychotherapy have shown robust efficacy in treating anxiety and depression and addiction to tobacco and alcohol. Psychedelic therapy may reverse the symptoms of complex psychiatric conditions. Psychedelic drugs, the so-called mind-expanding drugs, are able to induce states of altered perception and thoughts with a heightened awareness of sensory input.
Psychedelic drugs achieved their widest popularity during the 1960s when LSD was used to treat alcoholism. The changing view of psychedelics can be attributed to the renewed interest in their potential to treat mental health problems such as depression. The gradual transition of psychedelics, from dangerous to therapeutic, has been bolstered by a booming wellbeing industry. The word “psychedelic” is derived from Greek words which mean “mind-manifesting”. It refers to the ability of these compounds to bring hidden aspects of the subconscious mind into a conscious framework. Psychedelic compounds hold the potential as therapeutics for psychiatric disorders. Psychedelics result in profound changes in consciousness, perception, emotions, and self-awareness.
The renaissance of psychedelic research sheds light on the neurophysiology of altered states of consciousness induced by classical psychedelics, such as psilocybin and LSD. LSD has proved to be a potent drug that may induce sympathomimetic effects, such as an increased heart rate. Psychedelic drugs have been considered as treatment aids for psychotherapy, alcoholism, and mental disorders. Psychedelics that are considered as safe, efficient, and tolerant are 1) ketamine, psilocybin, and ayahuasca for recurrent and treatment-resistant Major Depressive Disorder (MDD) 2) MDMA and LSD for treatment-resistant post-traumatic stress disorder (PTSD) 3) psilocybin for obsessive-compulsive disorder (OCD) 4) alcohol abuse and 5) smoking cessation 6) ayahuasca for suicidality and 7) psilocybin and lysergic acid diethylamide (LSD) for anxiety, depression, pain.
How do These Drugs Work?
Scientists found that psychedelics reduced brain activity in the default mode network which is involved in a range of metacognitive processes. Psychedelics also have a strong reputation as a performance enhancer. Many famous musicians and artists have stated that microdosing using small doses to avoid large-scale effects can promote wellbeing, creativity, and productivity. Serotonergic psychedelics include the semisynthetic ergoline LSD, plant-derived tryptamines, such as psilocybin (the active ingredient found in “magic mushrooms”), N,N-dimethyltryptamine, 5-methoxy-N,N-dimethyltryptamine, and lysergic acid amide and phenethylamines, such as mescaline, and phenethylamine-based synthetic designer drugs. Serotonergic psychedelics are primarily found in nature (e.g., psilocybin, DMT, mescaline, and LSD). LSD can also be created in a laboratory by modifying natural psychedelics. Newer analogs of pharmacophore lysergamides, tryptamine, and phenethylamine structures are serotoninergic psychedelics that are considered as “nonclassical”. The therapeutic effects of psilocybin have yielded promising results for the treatment of depression, tobacco addiction, and OCD, as well as anxiety and distress associated with a life-threatening illness.
Today, hallucinogens are not classified as ‘psychosis inducers’ but instead are classified by their chemical structure, pharmacological mechanism of action, and clinical properties:
i. Classic psychedelics - These serotonergic hallucinogens are full or partial agonists of serotonergic 5-HT2A receptors. They include LSD, psilocybin, and N,N-dimethyltryptamine (DMT), all of which induce a state of altered perception, thought, and feeling.
ii. Empathogens/entactogens - Psychoactive substances that produce distinctive emotional and social effects. Methamphetamine (MDMA) is known to cause emotional connectivity as well as increased sociability and affability.
iii. Dissociative anaesthetics - Glutamatergic NMDA receptor antagonists such as ketamine, phencyclidine, and dextromethorphan (DXM) reduce excitation, causing sedation and perceptual distortion.
Effects of Psychedelics
Psychedelic Compounds as Immunomodulatory and Anti-Inflammatory Agents
Inflammation is a complex biological response which deals with the stressor and returns the system to homeostasis. Psychedelics profoundly affect inflammation and immunity and these effects are involved in the anxiolytic and antidepressant effects elicited by psychedelics. Notably, the anti-inflammatory and immunomodulatory effects of psychedelics suggest that they might be useful in “inflammaging”.
Magic mushrooms are wild or cultivated mushrooms that contain psilocybin, a naturally occurring psychoactive and hallucinogenic compound. Magic mushrooms are hallucinogenic drugs, meaning they can cause imaginary sensations that seem real but are not. The effects of magic mushrooms are believed to be influenced by environmental factors.
Apart from the improvement in depression, anxiety discussed so far, the enhancement of several behavioural, social, and cognitive domains has been reported after psychedelic exposure. These result in reduced psychological distress, decreased opioid dependence, decreased criminal behaviour, enhanced creative divergent thinking and problem-solving skills.
Psilocybin is the drug of choice in recent years for several reasons. It carries less cultural baggage than LSD. It also has strong safety data based on studies, and so the FDA has approved a small number of clinical trials. It should be pointed out that the efficacy of a psychedelic in treating a particular condition could be attributed either to a psychological effect or to actual physiologic adaptive changes in brain neurochemistry.
Under the condition of the large and growing problem of mental health disorders today, a new approach, such as psychedelic-assisted psychotherapy, may provide a solution to a problem that traditional pharmaceuticals could not solve. However, several concerns need to be kept in mind during the drug development of psychedelics. Mild to moderate acute physical side effects of psychedelic compounds have been reported in controlled clinical trials.