Scientific Literature on Relieving Emotional Upset:

• Psilocybin Microdosing Research

• Cannabis Research




As a clinician, I’ve assembled select citations from the most recent literature in regard to psilocybin microdosing, cannabis and specific cannabinoids, as they relate to the nervous system and brain health. I hope these will offer deeper perspectives for the choices you make.

– Becca

Psilocybin Research

Using Psilocybin for Mental Health Won’t Make You Feel Paranoid, New Study Says

A new study published by the American Medical Association in JAMA Psychiatry finds that single-dose psilocybin therapy does not increase the risk of paranoia and other transient thought disorders. The study, which analyzed data from clinical trials spanning several decades, also noted that while some adverse effects like headaches and nausea were reported, these were generally mild and resolved within 48 hours. The researchers emphasize the need for further investigation into managing these effects and the role of licensed therapists in such settings.

A recent study published in Frontiers in Psychology investigates the relationship between psilocybin, mindfulness, mystical-type experiences, and serotonin receptors in the brain. Following participants for three months after a macro-dose of psilocybin, the new findings indicate that the participants who report mystical-type experiences are more likely to have increased mindfulness abilities.

This is the first double-blind, placebo-controlled, randomized, within-subject study specifically investigating the effects of low doses of LSD on mood, emotion processing, and cognition.
According to one of the lead authors, Katrin Preller, neuropsychologist, University of Zurich:

“The amygdala, considered the emotion center of the brain, changed how it interacted with other brain regions in the microdosers, indicating the potential to better regulate negative emotions.”

After a pause of nearly 40 years in research into the effects of psychedelic drugs, recent advances in our understanding of the neurobiology of psychedelics, such as lysergic acid diethylamide (LSD), psilocybin and ketamine have led to renewed interest in the clinical potential of psychedelics in the treatment of various psychiatric disorders. Recent behavioural and neuroimaging data show that psychedelics modulate neural circuits that have been implicated in mood and affective disorders, and can reduce the clinical symptoms of these disorders.The amygdala is a key structure in serotonergic emotion-processing circuits. This study assessed the effects of acute administration of the hallucinogen psilocybin versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers. Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration.

The amygdala is a key structure in serotonergic emotion-processing circuits. This study assessed the effects of acute administration of the hallucinogen psilocybin versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers. Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration.

Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defenses. The purpose of the study was to test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo.

Cannabis Research

CBD has emerged as promising treatment candidate for Social Anxiety Disorder (SAD) and preliminary neuroimaging data suggests that CBD acts on the same brain regions known to be altered in SAD. Additionally, CBD may have key advantages over existing treatments, including a rapid course of action, reduced potential for abuse and drug interactions with alcohol and opioids, as well as fewer sedative and cognitive side effects.

In 2016 Walsh et al reviewed the literature on the use of MM (medical marijuana) for anxiety and concluded that evidence from cross-sectional studies generally supported the anxiolytic (anti-anxiety) effects of MM.

Pure THC appears to decrease anxiety at lower doses and increase anxiety at higher doses.

Cannabinoids are a unique class of chemical compounds incorporating plant‐derived cannabinoids (the active components of Cannabis sativa) the endogenous cannabinoids and synthetic cannabinoid ligands and these compounds are becoming increasingly recognized for their roles in neural developmental processes.
Endocannabinoids may play pivotal roles in at least some of these phases of neurogenesis. Of particular interest are the varying temporal effects of synthetic endogenous and plant‐derived cannabinoids on the proliferation and survival phases of neurogenesis indicating complex physiological regulation of this process that may be modulated by drugs that target the endocannabinoid system. The functional importance of neurogenesis has yet to be clarified however the weight of evidence indicates that impaired neurogenesis is associated with depression and cognitive impairment. Pharmacological targeting of the cannabinoid system as a regulator of neurogenesis may prove a fruitful strategy in the prevention or treatment of mood or memory disorders.

Similar to clinically used antidepressants cannabinoids can also regulate anxiety and depressive symptoms.

The putative role of cannabinoid in the control of mood and anxiety disorders has been describe by numerous authors [103 104]. In addition it has been suggested that the majority of the available treatments for depression modulates sendo-cannabinoid signaling.

Human experimental findings support preclinical findings and also suggest a lack of anxiogenic effects minimal sedative effects and an excellent safety profile. Current preclinical and human findings mostly involve acute CBD dosing in healthy subjects so further studies are required to establish whether chronic dosing of CBD has similar effects in relevant clinical populations. Overall this review emphasizes the potential value and need for further study of CBD in the treatment of anxiety disorders.

CBD’s therapeutic potential has been investigated in a number of neuropsychiatric diseases and pathological conditions. In the present preclinical review we provided an overview of behavioral and neuropharmacological studies that evaluated CBD as an anxiolytic- and antidepressant-like compound. Moreover we outlined evidence suggesting that CBD’s therapeutic-like properties may involve epigenetic mechanisms that include DNA methylation histone modifications and the regulation of miRNA expression. Collectively and given CBD’s safety profile these studies support the continued evaluation of CBD as a promising new agent in the treatment of anxiety and mood disorders. However future studies are still warranted to elucidate CBD’s precise pharmacodynamic profile and epigenetic mechanisms of action.

This 2019 Canadian study examined the prevalence of cannabis use for anxiety symptoms through a survey. About 900 (888) people who were using cannabis to treat anxiety symptoms responded about their medical use of cannabis (referred to as CMP – “cannabis for medicinal purposes”). Among the symptoms they reported included Generalized Anxiety Disorder, Social Anxiety Disorder, Major Depressive Disorder, Panic Disorder/Agoraphobia. Most (92%) reported that cannabis improved their symptoms. The vast majority perceived symptom improvement and did not believe it caused them impairment or an inability to control use.

This 2019 study out of Colorado was to determine whether CBD helps improve sleep and/or anxiety with varying doses of CBD from 25mg to 75mg/day. Seventy-two adults with either anxiety (47 of them) or trouble sleeping (25 of them) were given the CBD. After the first month the majority of patients experienced an improvement in anxiety and sleep. The sleep scores demonstrated mild improvement while anxiety scores decreased within the first month and remained so during the 3-month study duration. The conclusion quoted from the study: “Cannabidiol [CBD] may hold benefit for anxiety-related disorders. Controlled clinical studies are needed.”

This 2019 study out of Brazil confirms the anxiety-reducing properties of CBD.  Fifty-seven men were given none or various doses of CBD (150mg, 300mg, 600mg) and then performed a simulated public speaking test (SPST). This public speaking test a well known for its anxiety-inducing effects – as you can well imagine! Intriguingly, those taking the 300mg CBD had significantly reduced anxiety but not so with the placebo or the 150mg and 600mg. The researchers’ conclusion: “Optimal therapeutic doses of CBD should be rigorously determined so that research findings can be adequately translated into clinical practice.”

This 2019 Canadian study draws on data from a Community Health Survey of Mental Health (just regular people over 15 years old) and reports there is “compelling preliminary evidence from a general population sample that cannabis use modified the association between PTSD and depression and suicidality” meaning that cannabis reduced depression and suicidal inclinations among those who didn’t have a dependence on cannabis use. Researchers concluded: “There is an emerging need for high-quality experimental investigation of the efficacy of cannabis/cannabinoids for the treatment of post-traumatic stress disorder.”

This is a 2017 British overview of studies showing the anti-anxiety effects of CBD and focuses on the findings as they relate to reducing fear and processing addiction cravings. The study notes: “Converging lines of evidence have established that acute CBD treatment is anxiolytic [reduces anxiety] on both humans and animals.” and “In summary, this line of research may lead to the development of a formulation of CBD for use as a treatment for anxiety-related and substance abuse disorders in the future.”