Evidence on Psilocybin, Anxiety, and Depression

Given that serotonin plays a well-known role in human happiness, and given that psilocybin acts on serotonin pathways, it is hardly surprising that the psychedelic’s potential role in treating depression is a strong point of research interest. And in fact, there are multiple studies which point to promising evidence in support of this.

The beginning of this decade heralded one of the earliest legal pilot studies on psilocybin, depression, and anxiety. As with numerous other psychedelic research designs, it involved participants with pre-existing medical conditions – in this case, 12 volunteers with late-stage cancer and a related anxiety disorder. In comparing the impact of psilocybin on these participants’ mood disorder symptoms, Grob and colleagues’ (2011) found a noticeable downward trend in the severity of the treatment group’s anxiety and depression.

In other words, participants who had taken a moderate psilocybin dose had less serious symptoms at the 2-week mark than those in the control group – who were given a placebo. Though the difference only reached statistical significance at the 6-month mark–as can be expected with a very small number of participants–every month thereafter for half a year this trend continued. Most promisingly, there was no report of major adverse side effects – an interesting point when considered alongside the potential risks of benzodiazepines and other conventional antidepressants.

Grob and colleagues’ research findings received further support from the findings of more recent cancer patient studies. For example, with a larger sample size of 51 participants, Griffiths et al. (2016) expanded the research design to encompass two separate dosing sessions, each time with a different sized dose. In this set of studies:

Participants took both a high oral dose of psilocybin (22 or 30 mg grams per kilogram of body weight) and a very low dose (1 or 3 grams per kg) at a different date. The second served as a point of comparison, as with only trace amounts of psilocybin, no real effect was possible. It also acted as a control, to manage any potential effects from participants’ expectations.

When assessed up to five weeks after taking a high dose, patients showed significant improvements on multiple medical depression and anxiety scales, such as the Beck Depression Inventory, Hamilton Depression Rating Scale, and Hamilton Anxiety Scale.

Measured again at the six month mark, and perhaps most astonishingly, these improvements remained statistically significant. Around 60% of patients were no longer clinically depressed or anxious, and 80% continued to display reduced anxiety- and depression-related symptoms.

Similar results are continuing to emerge as increasing scientific interest and funding come to move the field forward. Examples include:

A 29-patient, 2016 study by Ross and colleagues, which compared psilocybin’s effects to niacin placebos, and followed psilocybin’s effects for over 6 months. This study of life-threatening cancer patients with related anxiety diagnoses supported Griffith et al.’s (2016) results. More than 60% of patients showed substantially reduced anxiety and depression symptoms up to 6 months after taking psilocybin. They also reported no serious adverse side-effects; and

Another slightly different pilot study by Carhart-Harris et al. (2016a) which examined 12 patients with treatment-resistant major depression. Unlike the prior two experiments, both patients and researchers were aware of what psilocybin doses were being administered (i.e., it was an “open label” design)- but similarly, they underwent two separate dosing sessions with different sized doses. As with the previous examples, participants’ depression and anxiety symptoms significantly improved by an average of 20 to 50%, and no major adverse side effects were noted. These results held three months after the psilocybin dosing.

Psilocybin and Substance Abuse

Substance use and misuse are frequently related to mood disorders. A large proportion of the time, abuse is a maladaptive coping strategy which can be hard to treat, often leading to dependence. Given that addict populations are commonly found to have lower serotonin levels, the potential use of psychedelics as a part of recovery has also been explored as restrictions have begun to ease. Some of the scientific results are indeed encouraging for those interested in new nicotine and alcohol dependence treatments, in particular.

Findings On Psilocybin and Smoking Cessation

First, there is some evidence that psilocybin, alongside Cognitive Behavioral Therapy (CBT), may be effective in helping people quit smoking. One study by Johnson and colleagues (2014) involved administering the psychedelic to 15 treatment-resistant smokers (informed volunteers) on the day they quit smoking. Results showed that:

80% of psilocybin-treated participants were biologically confirmed to be abstinent from smoking six months after their first dose;

This is substantially higher than traditional medication or behavioral studies, which typically result in a ~35% abstinence rate after six months; and

On top of this, follow-up studies 2.5 years later revealed that 60% of the participants were still non-smokers (Johnson et al., 2017).

For interested readers, Johnson and colleagues’ participants took the drug a total of three times; a fortnight after the initial dosing – the ‘target quit date’ – and then again at the eight-week mark. These second and third sessions involved higher psilocybin doses (30mg/70kg). Alongside these sessions, participants had 10 weeks of CBT, which has been shown to promote longer-term abstinence in smoking cessation programs (Killen et al., 2008).

How did participants describe their experience? And what were their thoughts about the psilocybin use and the impact on quitting? The answers are varied, according to interviews conducted by Noorani and colleagues (2018) – but interestingly, most described how the drug gave them “vivid insights into [their] self-identity and reasons for smoking.”

They also mentioned:

Feeling awe, interconnectedness, and curiosity which overshadowed their short-term nicotine withdrawal symptoms;

That these feelings lasted long after psilocybin’s immediate effects had passed;

That preparatory counselling and good support staff relationships helped them remain abstinent; and

That the study itself gave them momentum to remain abstinent over time.

Can Psilocybin Help with Alcohol Dependence?

There is also evidence suggesting psilocybin treatment may help to substantially reduce the frequency of binge-drinking behavior in alcohol-dependent individual. Bogenschutz and colleagues (2015) recruited a sample of alcohol-dependent participants to receive one or two psilocybin doses along with traditional 12-week Motivational Enhancement Therapy (a type of counseling designed to motivate patients to engage with treatment over time). ,

Ten participants were given an initial dose of psilocybin (0.3mg/kg) after 4 weeks of Motivational Enhancement Therapy and 24 hours after their last drink. Results showed that: