LSD

What is LSD-assisted therapy?

LSD-assisted therapy is an investigational treatment model: one or a few doses, given in a controlled clinical setting, with support before, during and after the session [2] [3]. It is not a daily medication.

The format varies. In some studies the experience is worked through afterwards in psychotherapy appointments [2]; in others psychotherapy is excluded and participants are simply monitored [4].

Results from one model therefore do not automatically carry over to the other.

What happens in a research protocol?

In trials, LSD is given in only a few sessions, usually one or two, always with professional support [3] [4]. Each session takes a full day and follows similar steps.

• Preparation: a medical and psychiatric assessment and preparatory sessions to build trust; some psychiatric medicines are tapered off beforehand [2] [15].
• The session: a safe physical setting, with at least two professionals present throughout [15] [4].
• Monitoring: blood pressure and heart rate are checked, adverse events are recorded and driving is not allowed afterwards [2].
• Integration: drug-free appointments to review and integrate the experience, in protocols that include psychotherapy [2].

Which conditions is it being researched in?

LSD has been researched mainly in anxiety, in controlled trials in Switzerland and the United States. Alcohol dependence was studied in older trials, and sponsor phase 3 data are still unpublished.

In generalised anxiety, a phase 2b trial found that a single dose reduced anxiety more than placebo, while the lower doses did not differ from placebo [4]. In the Swiss trials, the improvement lasted for months [2] [3].

The sponsor has reported its phase 3 studies as positive, but the data have not yet been published in peer-reviewed form [16] [9]. The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation, which speeds development but is not an approval [9] [18].

In alcohol dependence, the older trials linked a single dose to less problem drinking, but they have methodological weaknesses [17] [2].

What are the risks?

Visual changes and nausea are common while the drug is acting, and blood pressure and heart rate rise moderately [4] [10]. The most important risks are psychological.

• Overwhelming distress during the session, the most likely risk, which can lead to dangerous behaviour [15].
• Prolonged psychosis, which is less common [15].
• Persistent perceptual changes, in which visual effects return after the session; these are uncommon and reported mostly after illicit use [19].
• Interactions: a selective serotonin reuptake inhibitor antidepressant raised LSD concentrations [20]; low-quality reports link psychedelics taken with lithium to seizures [21].

Contraindications. Trials exclude people with a personal or family history of psychosis or other severe psychiatric illness, bipolar I disorder, current alcohol or drug dependence, pregnancy and breastfeeding [15] [2].

Outside a supervised medical setting, complications arise more easily [5].

What is its legal status?

LSD is a controlled substance internationally and in Portugal. No LSD medicine is approved in the European Union, Portugal or the United States.

• European Union: no LSD medicine has been evaluated by the European Medicines Agency [22]; internationally, it is in Schedule I of the 1971 Convention [8].
• Portugal: lysergide (LSD) is listed in Schedule II-A of Decree-Law 15/93 [23] [24]; decriminalising personal use did not make it legal [25].
• Switzerland: the Federal Office of Public Health can authorise limited medical use of LSD case by case, at the physician’s request and with the patient’s written consent [26] [27].
• United States: it remains in Schedule I [28]; the sponsor expects to apply to the FDA for approval in 2027 [9].

What is still being researched

Research on LSD is moving forward on several fronts. The next steps should clarify who benefits, for how long and under what conditions.

• Confirming phase 3: peer-reviewed publication and regulatory assessment of the reported results [9].
• The role of expectation: trial designs in which LSD’s obvious effects do not reveal group allocation [4] [29].
• How long benefit lasts: longer follow-up in larger groups [3] [2].
• What psychotherapy adds: comparing protocols with and without psychotherapeutic support [2] [4].
• Interactions: combination with other psychiatric medicines [20].
• Mechanism: how brain changes during the drug’s action relate to clinical benefit.