Rates of mental illness in youth have risen significantly in recent years. However, conventional treatments such as selective serotonin reuptake inhibitors (SSRIs) do not work effectively for every patient. Recent research suggests that recreational drugs can treat mental illnesses such as anxiety and post-traumatic stress disorder (PTSD). While the use of recreational drugs as medicine has been met with controversy, new research on psychopharmaceuticals is redefining the limits of mental healthcare.
LSD
Lysergic acid diethylamide (LSD) is a mind-altering substance that induces “trips”, which are characterized by hallucinations as well as time distortion. Discovered in the 1930s, LSD was widely used recreationally in the 1960s as an integral part of hippie culture. More specifically, the drug affects the serotonin receptors in the brain that are responsible for stabilizing mood and emotions. Disruptions in the functioning of these receptors are often associated with psychiatric diseases such as schizophrenia, depression, and anxiety.
LSD has been shown to improve social behaviour, as measured by the number of interactions between individuals. According to Dr. Danilo De Gregorio, a postdoctoral fellow in McGill’s Department of Psychiatry, the drug could mitigate many psychiatric diseases, such as autism and social anxiety, of which symptoms include a lack of voluntary socialization.
“Hallucinogenic compounds such [as] LSD being able to increase sociability may help to better understand the pharmacology and neurobiology of social behaviour and, ultimately, to develop and discover novel and safer drugs for mental disorders,” De Gregorio wrote in an email to The McGill Tribune.
However, De Gregorio’s research on LSD yielded no evidence of its efficacy as an antidepressant. The use of LSD in minuscule doses could alleviate social anxiety, but shows little potential as a treatment for depression.
LSD targets serotonin receptors found in the medial prefrontal cortex (mPFC), an area of the brain that regulates social information as well as memory. When studying the injuries to different areas of the mPFC, researchers found that lesions to the cortex led to social apathy. When administered to mice, LSD causes short bursts of activity in specific neurons that activate a protein complex called mTORC1, which may be blocked in individuals with social anxiety.
“We found that LSD exerts prosocial effects via a protein complex, the mTORC1, which we previously demonstrated to be dysregulated in pathologies with social deficits,” De Gregorio wrote.
Ketamine, a non-psychedelic drug used for anesthesia—and recreationally—was also shown to exhibit antidepressant effects through the activation of mTORC1.
Psilocybin
Psilocybin is a psychoactive drug that causes visual and auditory hallucinations. Like LSD, it is classified as a psychedelic and has similar mind-altering properties. As one of the main compounds in magic mushrooms, psilocybin has been studied since the 1990s for its ability to treat psychiatric diseases.
Psilocybin, like LSD, works by targeting serotonin receptors in the brain. More precisely, it increases the activity of specific serotonin receptors which are associated with somatosensory inputs and controls the way a patient processes sensory information. One study suggests that this alteration to sensory regions could help to mitigate substance abuse disorders.
While psilocybin and LSD target the same receptors, they have different effects on mPFC neurons. LSD was found to control parts of the brain involved in emotional processing, including the mPFC-amygdala circuit. Psilocybin desynchronizes the activity between the mPFC and the posterior cingulate cortex, reducing their functional connectivity and contributing to different perceptions of reality.
The drug can also rewire the brain by changing neural firing patterns, or the groups of cells that are transmitting information at a given time.
“In parts of the brain that usually do not communicate together, [the neurons] will fire together [when psilocybin is given],” Dr. Natalie Gukasyan, a postdoctoral fellow at Johns Hopkins’ Center for Psychedelic and Consciousness Research, said in an interview with the Tribune.
Psilocybin also changes the way the thalamus, the part of the brain responsible for relaying sensory information to different processing regions, responds to different inputs. While the substance can induce a “bad trip”, hallucinations about a physically uncomfortable or anxiety-inducing experience can assist patients in overcoming it.
“In most cases […] it does not mean that the [patient] will have a negative long-term outcome [….] They might come out with a sense of mastery [of their experience],” Gukasyan said. “However, a challenging experience in the lab or in a clinic is different than [one] in a non-supported environment.”
When psilocybin is administered in a monitored, clinical setting, the results are promising. Without the support of healthcare professionals or dosage control, the drug can exacerbate a patient’s mental health problems.
This treatment could alleviate conditions such as PTSD by dampening the fear response associated with traumatic memories.
Future research is needed to determine the appropriate dosing of this psychedelic. Too little does nothing to help the patient, yet too much could be dangerous for their health. Further studies are necessary to investigate the anti-inflammatory effects of the drug and how this property could be used to treat several inflammatory and auto-immune disorders such as rheumatoid arthritis.
Cannabidiol (CBD)
Cannabidiol, better known as CBD, is a derivative of the Cannabis sativa plant that has been shown to affect serotonin transmitters and reduce anxiety symptoms in rats. Unlike tetrahydrocannabinol (THC), which is the psychoactive component of cannabis, CBD does not induce paranoia or hallucinations. It is currently commercially available across Canada.
One study found that CBD blocks receptors that mediate pain sensations. CBD made the serotonergic neurons less likely to be activated and produced an anti-anxiety effect on the model rats.
Much of the research on CBD, however, has only been performed using animal models. Dr. Irina Kudrina, assistant professor in McGill’s Department of Family Medicine, notes that it is difficult to parse out CBD’s specific effects on humans.
“Cannabidiol (CBD) is one of many plant-derived biologically active molecules that, when a cannabis-based product is used, act synergistically,” Kudrina wrote in an email to the Tribune. “This synergy makes a ‘pure’ CBD effect difficult to discern. As cannabis research in humans is still in its infancy, our understanding of how this specific plant molecule interacts with the animal neurochemical system is quite limited.”
One study suggests that single, high doses of CBD have little effect on anxiety, depression, or psychosis, but if given at low doses for a limited period of time, it could have therapeutic properties.
In a different study, CBD was also shown to decrease the stress response symptoms of PTSD by blocking the reconsolidation of traumatic memories and modulating the endocannabinoid system, which contains built-in receptors to CBD and regulates memory and anxiety.
“[O]ur endogenous cannabinoid system constitutes one of the biggest and complex neuro-endocrine systems playing an important role in the development and further functioning of the human memory, learning, sleep, [and] emotional and behavioural mechanisms, to name a few,” Kudrina wrote.
CBD also inhibits regions of the brain that are hyperactive in PTSD patients, such as the amygdala, the part of the brain responsible for the body’s fear and stress responses.
Further research is required to destigmatize the recreational use of CBD and expand upon existing treatments for mental illnesses such as anxiety disorders.
“To date, the data pointing at some anti-stress and anti-anxiety properties of CBD are still insufficient and controversial,” Kudrina wrote. “Nonetheless, the body of research on the clinical usage of CBD in these areas is growing quickly.”
