Psilocybin

What does treatment look like in trials?

In trials, psilocybin is synthetic, given as capsules at a fixed dose, not as mushrooms [2] [29]. Treatment has three stages:

• Screening and preparation. A medical and psychiatric assessment, with an electrocardiogram and blood tests, and several hours of discussion to explain the effects and build trust with the team [9] [23].
• Session. This takes place in a quiet room, with at least two professionals present and blood pressure and pulse monitored [9]. Effects begin within an hour and fade to minimal levels after about six hours; the session usually lasts about eight [14] [11].
• Integration. Later meetings, without the drug, to make sense of the experience and connect it with everyday life.

The type of support varies between studies, from psychological support to structured psychotherapies such as motivational enhancement and cognitive behavioural therapy [1] [30].

Which conditions is it being researched in?

Depression is where psilocybin therapy has the strongest evidence, particularly treatment-resistant depression [1]. In other conditions, research is still at an early stage.

Treatment-resistant depression. In 2022, a single dose reduced symptoms at three weeks compared with a minimal control dose, but without a clearly sustained response at three months [2]. In 2025 and 2026, the sponsor announced favourable phase 3 results against comparators, not yet published in peer-reviewed form [19] [20]. A German phase 2b trial, published in 2026, missed its primary endpoint [31].

Major depressive disorder. In the United States, a single dose reduced symptoms more than an active placebo [29]; in the United Kingdom, it did not differ significantly from escitalopram on the primary outcome [3]. A 2024 meta-analysis found a benefit over comparators, larger in people who had used psychedelics before, so the role of expectations needs to be clarified [38].

Other areas. In alcohol use disorder, psilocybin reduced heavy drinking days compared with an active placebo [30]. The studies in smoking, obsessive-compulsive disorder and anorexia nervosa are there to inform larger trials, not to establish indications.

What are the risks and contraindications?

Under controlled conditions, the most common adverse effects are acute and short-lived: headache, nausea, dizziness and anxiety as the effects begin [2] [14]. Blood pressure and pulse rise moderately [9].

Some signals need attention. In a 2022 trial, suicidal ideation or self-injury occurred in every group [2], and in the 2026 German trial suicidal ideation on dosing days was more frequent with the higher dose [31]. Adverse effects are probably under-reported in these studies [39].

Trials usually exclude:

• a personal or family history of psychosis or another severe psychiatric disorder [9];
• a history of mania, active suicidal ideation with intent, or active substance use [29];
• raised blood pressure, assessed with physical examination and electrocardiogram [9];
• pregnancy [9].

Interactions. Several trials required psychiatric medicines to be tapered and stopped before the session [29] [31]. Escitalopram dampens some of the effects of psilocybin [40], and combining classic psychedelics with lithium has been linked to seizures [41] [42]. Any change to medication is a medical decision.

Unsupervised use. In a survey on difficult experiences with mushrooms, a minority reported physically risky situations or sought help for persisting symptoms; risk was linked to dose and lack of support [43]. In studies with screened and supported participants, such problems are extremely rare.

What is the legal status of psilocybin?

Psilocybin is not an authorised medicine in the European Union: the European Medicines Agency has not authorised any medicine containing it [44]. Psychedelics follow the same rules as all medicines and must show a positive benefit–risk balance [45].

In Portugal, psilocybin and psilocin are controlled substances, listed in the schedules of Decree-Law 15/93 [46]. There is no authorised medicine and no clinical access scheme.

Elsewhere, access routes exist and differ from one another:

• Australia. Since July 2023, psychiatrists authorised by the medicines regulator may prescribe psilocybin for treatment-resistant depression; the regulator has not evaluated any product for quality, safety and efficacy [18].
• Czechia. Since January 2026, the law has allowed restricted medical use in adults, as a compounded medicine prescribed by psychiatrists and given in healthcare facilities, mainly for severe depression where authorised medicines have failed. Availability in practice is not yet confirmed [22].
• United States. No psilocybin medicine has been approved by the FDA; the marketing application under way is not an approval [21]. Oregon runs a state psilocybin services programme that is not a medical treatment [47].

An authorisation in another country has no effect in Portugal.

What is still being researched

Research is now focused on questions that will shape the place of psilocybin in clinical practice. The main ones are:

• How long benefit lasts. How long improvement holds after a session, with longer follow-up [2].
• Blinding and expectations. How to design trials in which participants cannot easily tell which group they are in [48] [38].
• The role of psychotherapy. How much of the effect depends on psychological support, and which model of support suits best [1].
• Comparison with established treatments. Larger and longer trials against antidepressants [3].
• More diverse populations. Results in less selected patients, closer to everyday practice [1].
• Long-term safety. Detecting rare adverse effects as more people are treated [39].