Key Psychedelic Deep Dives – PSYCH: The Psychedelics As Medicine Report 3rd Edition

The following psychedelic deep dives provide detailed insight into current clinical research, regulatory status, and therapeutic potential across the leading psychedelic compounds being studied globally.

Each section summarises clinical trial progress, geographic research activity, and the evolving legal frameworks shaping access to these substances.

• Psilocybin
• LSD
• MDMA
• Ketamine
• Ibogaine
• Ayahuasca

Psilocybin

Overview and key developments

Psilocybin-assisted therapy for depression, including major depressive disorder (MDD) and treatment-resistant depression (TRD), is completing phase II clinical trials and may become a licensed therapy as early as 2025.

Academic studies worldwide using psilocybin with accompanying psychological support are demonstrating rapid and long-lasting positive effects in patients with depression and anxiety. In one long-term follow-up study, benefits remained evident up to four and a half years after treatment.

Alongside healthcare-reimbursed models, decriminalisation initiatives are opening parallel pathways for psilocybin (commonly referred to as “magic mushrooms”) to be explored as tools for improving mental wellbeing.

Clinical trials and research

Psilocybin is the second most studied psychedelic after ketamine. As of July 2021, there have been 64 clinical trials, including 26 phase II studies, enrolling nearly 2,100 patients.

Clinical and academic research suggests potential therapeutic benefit for:

• Depression (MDD, TRD, and bipolar disorder)
• Anxiety and depression in patients with life-threatening illness
• Social anxiety in autism
• Substance misuse (alcohol, nicotine, opioid dependence)
• Eating disorders, including anorexia nervosa
• Demoralisation in long-term AIDS survivors
• Cluster headaches and migraines
• Obsessive-compulsive disorder (OCD)

Regional research highlights

In North America, landmark studies at Johns Hopkins University and New York University have demonstrated durable reductions in depression, anxiety, and substance dependence, with low abuse potential relative to conventional treatments.

European research has been led by institutions including Imperial College London and King’s College London, where psilocybin has shown the potential to “reset” dysfunctional brain networks in TRD patients.

In Oceania, Australian research initiatives have been accelerated through AU$15 million in federal funding supporting trials in psilocybin and MDMA.

Legal status

Under the 1971 UN Convention on Psychotropic Substances, psilocybin is classified as Schedule I. However, ambiguity around naturally occurring psilocybin-containing fungi has resulted in varied national approaches.

Decriminalisation initiatives across US cities and states, Canada’s Section 56 exemptions, and regulated therapeutic frameworks such as Oregon’s Measure 109 illustrate shifting policy approaches.

LSD (Lysergic Acid Diethylamide)

Overview and key developments

LSD was extensively studied during the 1950s and 1960s, generating over 1,000 scientific publications. Research from that period suggested benefits in end-of-life anxiety, depression, and alcoholism.

Modern research using neuroimaging has deepened understanding of how LSD alters consciousness by reducing hierarchical brain control and increasing network connectivity.

The long duration of LSD experiences limits its practicality as a mainstream medicine, though its potency and microdosing applications continue to attract research interest.

Clinical trials and research

As of July 2021, 19 clinical trials involving LSD have been conducted, including four phase II studies, enrolling approximately 530 participants.

Conditions under investigation include:

• Depression (MDD)
• Anxiety associated with life-threatening illness
• Substance misuse (alcohol, nicotine, opioids)
• Alzheimer’s disease (low-dose LSD)
• Cluster headaches and migraines
• Obsessive-compulsive disorder (OCD)

Legal status

LSD remains a Schedule I substance under the UN Convention on Psychotropic Substances. However, possession of small quantities has been decriminalised in jurisdictions such as Oregon, Mexico, and Portugal.

MDMA

Overview and key developments

MDMA is classified as an empathogen rather than a classic psychedelic. It produces limited hallucinogenic effects and has a higher recreational abuse potential than classical psychedelics.

MDMA-assisted psychotherapy for PTSD has completed the first half of phase III clinical trials and received FDA Breakthrough Therapy designation in 2017. Full approval is anticipated in 2023.

Clinical trials and research

As of July 2021, MDMA has been studied in 47 clinical trials, including three phase III studies, enrolling nearly 1,900 patients.

PTSD research led by MAPS has demonstrated that 67% of participants receiving MDMA-assisted therapy no longer met diagnostic criteria for PTSD, compared with 32% in placebo groups.

Legal status

MDMA remains a Schedule I substance internationally, though several countries have decriminalised possession of small amounts. Germany permits possession of up to five grams for personal use, while Peru enforces far stricter thresholds.

Ketamine

Overview and key developments

Ketamine differs from other psychedelics in that it has been legally used as a general anaesthetic for decades and is included on the World Health Organization’s List of Essential Medicines.

Ketamine is widely used off-label for depression, anxiety, and suicidal ideation, with rapid onset of effects.

Clinical trials and research

Ketamine is the most studied psychedelic to date, with over 140 clinical trials excluding anaesthetic studies, enrolling nearly 11,000 patients as of July 2021.

Research supports ketamine’s efficacy across depression, suicidal ideation, PTSD, substance misuse, chronic pain, inflammation, and OCD.

Legal status

Ketamine is classified as a Schedule III drug in the US and a Class B drug in the UK, remaining legally available for medical use in most countries worldwide.

Ibogaine

Ibogaine is a naturally occurring psychoactive compound traditionally used in West Africa and increasingly explored for substance use disorders. While not scheduled under UN conventions, it is illegal or tightly controlled in many Western countries.

Observational research indicates ibogaine may reduce opioid, cocaine, and alcohol misuse after a single dose, though cardiovascular risks have limited wider clinical adoption.

Legal status

Ibogaine therapy operates in legal or grey-market settings in countries including Mexico, Portugal, and New Zealand, with treatment costs typically ranging from US$5,000 to US$8,000.

Ayahuasca

Ayahuasca has been used in Latin America for over a millennium and has shown promise in treating depression, PTSD, and substance use disorders. Therapeutic outcomes are closely linked to ceremonial context and setting.

Only a small number of controlled clinical trials have been conducted, with one phase II study demonstrating rapid reductions in treatment-resistant depression.

Legal status

While DMT is a Schedule I substance under international law, ayahuasca’s plant components are not regulated. Religious exemptions in the US, Canada, and elsewhere allow ceremonial use under specific conditions.