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  • Writer's picturejessicascheufen

Over the counter and outside the box

Updated: Apr 12, 2022

To continue our discussion on the legalization of psychedelics for medical use in Canada, I will now discuss the neuropharmacology of psychedelics- how the drugs act on your brain. With an understanding of how these drugs work, we can explore how they may contribute to the treatment process for certain mental illnesses. Psychedelics may be an unorthodox approach when it comes to treating mental illness, however they share the common ability to reframe your perception of the world and its challenges.

Original image by Pixabay

Psilocybin- Magic Mushrooms

Psilocybin is the psychoactive molecule in magic mushrooms, meaning it is responsible for the hallucinogenic effects you may experience when you take them. Psilocybin does this by binding to serotonin receptors on neurons in your brain (1). This means it can influence the serotonergic system in many different brain regions. It is important to note that increased serotonin does not equal happiness. The serotonergic system is neuromodulatory, meaning it can influence pre-existing processes in many areas of your brain. Some of serotonin’s key roles are that it helps you to adapt behaviour following environmental changes (2), it helps you to form emotional memories (3), and it helps regulate emotions (4-6).

Psilocybin is coming forth as a potential treatment for many different mental illnesses, due to its ability to promote resilience. It does so by helping people regulate emotions and adapt to environmental changes. It has also been shown to increase feelings of connectedness and acceptance (7). Promising research has shown psilocybin to be an effective treatment for substance use disorders (1), treatment-resistant depression (8), anxiety disorders, and obsessive-compulsive disorder (OCD) (9).

MDMA- Molly

MDMA, commonly referred to as molly or ecstasy, is an amphetamine stimulant that is also classified as a psychedelic. Like psilocybin, it exerts its affects on your brain by acting on the serotonergic system. MDMA blocks the reuptake of serotonin back into your neurons, making it more readily available for action in your brain. In addition to serotonin, MDMA blocks reuptake of dopamine, which is responsible for producing reward, and norepinephrine, which can increase energy (10). Taking MDMA also leads to the release of oxytocin, which can produce feelings of love and empathy (11).

Image by Nature

This MDMA-induced increase in available serotonin, dopamine, and norepinephrine leads to emotional and cognitive changes such as increased euphoria and empathy. These effects have led researchers to explore MDMA as a potential treatment for treatment-resistant post-traumatic stress disorder (PTSD) (12). Notably, an increase in empathy has shown to allow people with PTSD to have an understanding and acceptance of their previous trauma. It has also been shown to aid patients in the discussion of past trauma during psychotherapy.

LSD- Acid

LSD is a hallucinogenic psychedelic commonly known as acid. Like the previously discussed drugs, LSD acts on serotonin receptors and dopamine receptors (13). Although the neuropharmacology of LSD still has a lot of grey area, it is thought that the effects of LSD on the serotonergic system increases brain connectivity in sensory areas, which explains why LSD produces sensory hallucinations (13). The “trips” experienced when hallucinating on acid are known to alter perception, thoughts, self-awareness, and mood (14).

The use of LSD for medical treatment currently has less available potential than psilocybin or MDMA due to lack of research. However, one study has shown that, like MDMA, LSD can also assist in psychotherapy (15). Particularly, this study found LSD may aid in the treatment of depression and PTSD, due to its ability to induce an altered state of consciousness. It does so by increasing the amount of serotonin available. This new state of consciousness is one in which patients have improved mood during psychotherapy and are more open to changing their thoughts and behaviours. More research is needed to determine the efficacy of LSD in assisting psychotherapy.

Now that we have a general understanding on the way these drugs work in our brain, we can understand why they might have therapeutic benefits. These psychedelics share the common mechanism of altering your perception and attitude in a way that can make you more resilient and understanding when battling mental illness. Stay tuned next week for a discussion on women in psychedelics research.

Written by Jessica

Note: Psychedelics are not currently available as over the counter medication. There is an extensive process required before being prescribed psychedelics, which will be discussed more in future posts.


1. De Veen BT, Schellekens AF, Verheij MM, Homberg JR. Psilocybin for treating substance use disorders?. Expert review of neurotherapeutics. 2017 Feb 1;17(2):203-12.

2. Davidson MC, Amso D, Anderson LC, et al. Development of cognitive control and executive functions from 4 to 13 years: evidence from manipulations of memory, inhibition, and task switching. Neuropsychologia. 2006;44(11):2037–2078.

3. Bocchio M, Fucsina G, Oikonomidis L, et al. Increased serotonin transporter expression reduces fear and recruitment of parvalbumin interneurons of the amygdala. Neuropsychopharmacology. 2015;40(13):3015–3026.

4. Lee TT-Y, Redila VA, Hill MN, et al. Receptor mediated neuronal activation within the paraventricular nucleus of the hypothalamus is desensitized following prolonged glucocorticoid treatment. Eur J Pharmacol. 2009;602(1):54–57.

5. Carrasco GA, Van de Kar LD, Sullivan NR, et al. Cocaine-mediated supersensitivity of 5-HT2A receptors in hypothalamic paraventricular nucleus is a withdrawal-induced phenomenon. Neuroscience. 2006;143(1):7–13.

6. Sotelo C, Cholley B, El Mestikawy S, et al. Direct Immunohistochemical evidence of the existence of 5-HT1A autoreceptors on serotoninergic neurons in the midbrain raphe nuclei. Eur J Neurosci. 1990;2(12):1144–1154.

7. Watts R, Day C, Krzanowski J, Nutt D, Carhart-Harris R. Patients’ accounts of increased “connectedness” and “acceptance” after psilocybin for treatment-resistant depression. Journal of humanistic psychology. 2017 Sep;57(5):520-64.

8. Carhart-Harris RL, Bolstridge M, Day CM, Rucker J, Watts R, Erritzoe DE, Kaelen M, Giribaldi B, Bloomfield M, Pilling S, Rickard JA. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology. 2018 Feb;235(2):399-408.

9. Daniel J, Haberman M. Clinical potential of psilocybin as a treatment for mental health conditions. Mental Health Clinician. 2017 Jan;7(1):24-8.

10. De la Torre R, Farré M, Roset PN, Pizarro N, Abanades S, Segura M, Segura J, Camí J. Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Therapeutic drug monitoring. 2004 Apr 1;26(2):137-44.

11. Sessa B, Nutt D. Making a medicine out of MDMA. The British Journal of Psychiatry. 2015 Jan;206(1):4-6.

12. Morgan L. MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn’t. Annals of General Psychiatry. 2020 Dec;19(1):1-7.

13. Preller KH, Burt JB, Ji JL, Schleifer CH, Adkinson BD, Stämpfli P, Seifritz E, Repovs G, Krystal JH, Murray JD, Vollenweider FX. Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. Elife. 2018 Oct 25;7:e35082.

14. Marona-Lewicka D, Thisted RA, Nichols DE. Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis. Psychopharmacology. 2005 Jul;180(3):427-35.

15. Schmid Y, Gasser P, Oehen P, Liechti ME. Acute subjective effects in LSD-and MDMA-assisted psychotherapy. Journal of Psychopharmacology. 2021 Apr;35(4):362-74.

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