Psilocybin vs ketamine: a tale of two therapies for depression

When standard antidepressants don’t bring relief, many Canadians begin exploring mental health alternatives. Two therapies in the spotlight are psilocybin-assisted therapy and ketamine treatment. Both are being studied for treatment-resistant depression, but they’re not the same journey.

Psilocybin sessions (still experimental in Canada) can open profound new perspectives, while ketamine therapy offers rapid but short-lived relief through legally available clinics. Here’s a clear-eyed comparison of psilocybin vs ketamine: how each works, the Canadian legal landscape, what the therapy experience is like, and what research says about their pros and cons.

How psilocybin and ketamine work in the brain

Psilocybin, found in certain mushrooms, is turned into psilocin in the body. It gently taps into your brain’s serotonin system—the same system linked to mood and well-being. This can quiet down the “mental chatter” that keeps people stuck in negative loops, opening space for new perspectives and emotional breakthroughs, especially when paired with therapy.

Ketamine takes a different route. Instead of serotonin, it activates your brain’s glutamate system. Picture it like watering a dry forest—ketamine sparks a burst of activity that helps the brain grow fresh connections more quickly. This is why many people feel relief within hours, even when other treatments have taken weeks.

In short: psilocybin may offer a deep reset with lasting effects, while ketamine is more like a fast-acting boost. Both give the brain a chance to step out of old patterns and into new possibilities.

Legal status in Canada

Here’s where the paths diverge:

• Ketamine: Available now. Health Canada approved an esketamine nasal spray for treatment-resistant depression in 2020. Dozens of clinics across Canada offer ketamine infusions or nasal therapy under medical supervision.
• Psilocybin: Still experimental. Psilocybin is a controlled substance in Canada, but it’s being studied in psilocybin clinical trials at institutions like CAMH. As of 2024, only a limited number of patients have received legal access through these routes.

In short: ketamine is a therapy Canadians can access today, while psilocybin is only available in regulated studies or on a case-by-case exemption basis.

What a treatment session looks like

Psilocybin therapy:

• Involves careful preparation with trained therapists
• A session lasts 4–6 hours in a calm, supportive setting
• Patients often wear eyeshades, listen to music, and focus inward
• Follow-up integration sessions help process the experience

Ketamine therapy:

• Usually delivered as a series of shorter sessions (40–120 minutes each)
• Administered by IV infusion, injection, or nasal spray in a clinic setting
• Effects begin within minutes, with a dreamlike, dissociative state
• Relief is often noticeable within hours, though it typically fades in days to weeks

Both therapies emphasise “set and setting”. The mindset you bring and the environment around you are crucial for positive outcomes.

Pros and cons of each approach

Psilocybin

Pros:

• Promising research shows sustained improvements lasting weeks to months after just one or two sessions
• Can catalyse meaningful emotional or spiritual breakthroughs
• Low physiological risk and non-addictive when supervised

Cons:

• Still illegal outside trials or exemptions in Canada
• Experiences can be emotionally intense, sometimes overwhelming
• Evidence base is still growing; long-term outcomes remain under study

Ketamine

Pros:

• Fast-acting—relief can come within hours, ideal in crisis situations
• Available now in Canada through clinics
• Research-backed safety profile in medical settings

Cons:

• Benefits usually short-lived without repeat treatments
• Multiple sessions can be costly and time-consuming
• Side effects may include nausea, dissociation, or blood pressure spikes

Canadian research and clinics leading the way

Canada is at the forefront of this exploration:

• CAMH in Toronto is running government-funded trials testing psilocybin for depression, including whether the psychedelic experience itself is necessary for benefits.
• Numinus and Mindspace clinics in Montreal and Vancouver are pioneering ketamine-assisted therapy and have also facilitated psilocybin therapy through Health Canada’s Special Access Program.
• Innovative studies like the Montreal Model combine ketamine with psychotherapy and soothing settings, showing longer-lasting results than ketamine alone.

These efforts are pushing psychedelic therapy from fringe to credible, evidence-based practice.

Where microdosing fits in

Full therapy sessions aren’t the only way Canadians are exploring psilocybin. Microdosing—taking very small, sub-hallucinogenic amounts—has become a gentle option for wellness-seekers. While science is still emerging, many adults report improved mood, focus, and creativity.

At Path Supply, we make it simple to explore this approach responsibly. Our psilocybin microdose capsules and edibles offer consistent dosing. No need to worry about grinding, measuring, or storing loose mushrooms. For those who aren’t eligible for clinical psilocybin therapy, microdosing provides a mindful, everyday way to see how psilocybin might support your path.

Final take

When comparing psilocybin vs ketamine, it’s not about which therapy “wins,” but how each might serve different needs. Ketamine is a rapid-acting option available now through Canadian clinics, though its benefits often require ongoing treatments. Psilocybin, still in trials, shows promise for longer-lasting effects after only a few sessions—but access is currently limited.

For Canadians curious about psychedelic therapy, the future is bright. With ongoing studies at CAMH and forward-thinking clinics like Numinus, more options are on the horizon. In the meantime, microdosing offers a safe, everyday entry point into psilocybin’s potential.

Whichever path you choose, do so with curiosity, care, and the right support. Healing is an adventure—and mushrooms can help guide the way. Choose your path.