The Science Behind Psychedelic Therapy for Depression

Psychedelic is a dissociative anesthetic that has gained attention for its potential role in treating treatment-resistant depression (TRD). While it was originally developed in the 1960s as an anesthetic, emerging research has explored its use—at sub-anesthetic doses—for individuals who have not responded to traditional antidepressants.

Psychedelic exerts its effects through several mechanisms, including dissociation, analgesia, and transient changes in perception. These effects have made it a valuable tool not only in operating rooms but also in select psychiatric and pain management settings. Although psychedelic is chemically related to phencyclidine (PCP), it has a safer profile and has been used in medical settings for decades.

What is psychedelic therapy?

Psychedelic therapy refers to the off-label administration of psychedelic —often intravenously—in a controlled medical setting, typically in combination with psychological support. It is being investigated as a rapid-acting option for those with severe depression, especially TRD, which is defined as a failure to respond to at least two adequate trials of antidepressants.

The dissociative properties of psychedelic may temporarily allow individuals to access distressing thoughts or emotions with less psychological resistance. In clinical settings, this experience is closely monitored to ensure safety and therapeutic benefit.

What is the science behind psychedelic therapy?

Espsychedelic , a derivative of psychedelic , has received FDA approval in the U.S. for use in TRD and is administered intranasally under strict protocols. Racemic psychedelic (the IV form) is still considered “off-label” for depression, though it is widely used in clinics.

Research has shown that psychedelic can lead to rapid but temporary improvements in mood, especially in those with suicidal ideation. However, results vary between individuals, and more research is needed to fully understand the long-term safety and optimal treatment protocols.

What reactions does it elicit in the brain?

Psychedelic's mechanism of action is not fully understood. It is known to affect multiple brain pathways and receptor systems:

• Glutamate modulation: Psychedelic influences the brain’s glutamate system by blocking NMDA (N-methyl-D-aspartate) receptors. This may lead to increased activity at AMPA receptors and downstream effects such as synaptic plasticity and neuronal communication.
• Neuroplasticity: Preclinical studies and some clinical evidence suggest psychedelic may stimulate the growth of new synaptic connections. This is of particular interest in patients with depression, where stress-related neuronal atrophy may be present.
• Rapid onset: Unlike traditional antidepressants, which can take weeks to work, psychedelic has been shown in some studies to reduce depressive symptoms within hours in certain patients.

Psychedelic Therapy’s Effects on Treating Depression

In Canada, up to 21.7% of individuals with depression may meet criteria for TRD. These individuals often experience prolonged episodes and may not respond to conventional antidepressants. For select patients, psychedelic therapy may offer a new pathway when other methods have not been effective.

By promoting this new growth, psychedelic may assist in treating depression.

Is psychedelic therapy safe?

Psychedelic therapy is generally well-tolerated in a controlled clinical setting, but it is not without risks. Common side effects may include nausea, dizziness, transient dissociation, elevated blood pressure, and perceptual disturbances.

While psychedelic is not physically addictive in the way that opioids are, repeated or unsupervised use carries the potential for psychological dependence. Recreational misuse can lead to significant cognitive, urological, and psychological harms.

For these reasons, psychedelic therapy should only be administered under the supervision of qualified healthcare professionals in an appropriately equipped clinical environment.

Important Caveats

• Not first-line treatment: Psychedelic is typically considered after other treatments have failed.
• Short-term relief: Benefits may be temporary, and maintenance strategies (such as integration therapy or booster sessions) are still under investigation.
• Long-term safety: More data is needed on the effects of prolonged psychedelic use for psychiatric purposes.

Contact Psychedelic Therapy Toronto to Discuss How We Can Help Treat Depression

Our clinic is dedicated to leveraging the success of psychedelic therapy to assist patients struggling with depression. Our experienced and well-trained medical team will ensure your safety throughout the process, conduct each procedure in a controlled clinical environment, and closely monitor you.

If you or someone you know is struggling with treatment-resistant depression, we invite you to contact Psychedelic Therapy Toronto to schedule a consultation. Our experienced medical team can help determine whether psychedelic therapy is appropriate for your situation. 

To see how we can assist you, call us at 647-259-7740 or email us at admin@psychedelic therapyclinic.ca to book your initial consultation. You can also contact us online.