Lysergic acid diethylamide (LSD) was synthesized by the Swiss chemist Albert Hofmann in 1938. In the early 1950s, a group of clinicians suggested that this hallucinogenic drug could be useful for mental health issues. Since the late 50s, other psychedelic compounds such as Psilocybin (AKA ‘magic mushrooms’), Mescaline, and DMT (N, N-dimethyltryptamine) have also been identified. These substances have been widely used in sacred ceremonies and ritual contexts in various cultures for many centuries. The widespread use of these drugs in the late 1950s brought about a revolution in psychiatry and brain science due to their positive results in treating alcohol use disorder, depression, anxiety, and psychosomatic diseases.
Two recent findings have led a renaissance in psychedelic research: (1) Griffiths and colleagues showed that a single high dose (25 mg) of Psilocybin induces positive mood changes and perceived well-being; (2) Neuroimaging studies by Carhart-Harris and colleagues have identified the impact of psychedelics on brain activity and their findings are similar to how antidepressants affect the human brain.
But what are Psychedelics and how do they work? Experts agree that psychedelics manipulate the brain’s response to the neurotransmitter Serotonin (5-Hydroxytryptamine, 5-HT) by activating the 2A receptors primarily expressed on neocortical pyramidal cells. Generally, the activation of 5-HT 2A receptors makes the host neuron more excitable. Researchers believe that this widespread increase in neural excitabilities particularly affects many brain regions (e.g., the medial prefrontal cortex, the reticular nucleus of the thalamus, ventral tegmental area, the locus coeruleus, amygdala, …) and gives rise to the perceptual and cognitive effects of psychedelics.
A commonly asked question about psychedelics is “What do they do to the brain and mind?” If we had to classify psychedelics’ effects on one’s mind and brain, the classification would potentially appear as i) perceptual effects, ii) cognitive effects, and iii) emotional effects.
Psychedelic-induced perceptual effects include perceptual intensification, distortion, illusions, mental imagery, elementary hallucinations, and complex hallucinations. People report things like: “Things looked strange” (illusions), “I saw movement in things that weren’t actually moving” (perceptual distortions), “I saw geometric patterns in objects” (elementary hallucinations), and “My imagination was extremely vivid” (mental imagery). The perceptual effects of psychedelics are highly dose-dependent and could be extremely varied.
The most common cognitive influence of psychedelics is acute changes in the normal flow of linear thinking (e.g., “My thoughts wandered freely”). Reduced performance of working memory and attention has been reported. Some say creativity can increase because several cognitive functions are enhanced under the influence of small amounts of psychedelics (e.g., average 0.37 grams of dried truffels). These include divergent thinking (thinking outside the box), problem-solving, cognitive flexibility, attribution of meaning to perceptual stimuli, and the subjective bizarreness and dreamlike nature of mental imagery associated with verbal stimuli. Notably, high doses of psychedelics could result in cognitive impairments. Some people have claimed that extremely low-doses– known as psychedelics miscrodosing can enhance cognitive enhancement but there is no systematic evidence for this claim.
Emotional effects of psychedelics –that are likely to be easily modulated by external stimuli such as music– are the intensification of feelings, emotional saliency, and conscious access to emotions. Most people say that they have positive experiences when “tripping“. But it is important to note that, negative senses such as fear, paranoia, and sense of losing control are also possible.
Many people suspect that psychedelics as extremely dangerous drugs of abuse. The fact is that experts consider them as physiologically safe. They do not produce dependence or addiction. In a way, knowing that serotonergic hallucinogens do not directly affect the brain’s dopaminergic system (i.e., reward and motivation system), this comes as no surprise that psychedelics are do not cause dependence and their impact is not addictive.
However, note that they are NOT risk-free: they can lead to mentally challenging experiences. The dangers with psychedelics are mainly psychological rather than physiological. For example, no overdose deaths have been reported after ingestion of typical doses of LSD, Psilocybin, or mescaline. But, erratic judgments (such as possessing superpowers or being invincible) have caused fatal consequences such as jumping off buildings, because the person tripping on the drug believed that they could fly. Johnson and Griffiths published safety guidelines for minimising such risks of hallucinogen administration.
The most critical concern about psychedelic research is that there are not that many field studies about them outside the controlled environment of labs. In addition, the lack of longitudinal study designs means that we know very little about their long-term effects.