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SSRI's Vs Psychedelics

SSRI's (Selective Serotonin Reuptake Inhibitors) in combination with CBT based psychotherapy are the mainstay of treatment for depressive and anxiety disorders. Unfortunately, the HSE trains and employs so few psychotherapists that there are huge waiting lists acting as a barrier to accessing psychotherapy. This means that we have come to rely more and more on SSRI's as the sole therapy for these mental health issues. In some cases, SSRI's alone may be enough of a help to get a person through a rough patch, allowing them to suffer less severely from their depressive or anxiety symptoms while they are waiting for some particularly painful circumstances to pass. For others, SSRI's are not enough to provide any significant relief as their issues may be more complex or severe. They may try another antidepressant medication such as an SSRI/SNRI/NaSSA/TCA/MAOI. If this does not work, the person's depressive or anxiety disorder is described as 'treatment resistant'.



People with treatment resistant disorders will stay in the psychiatric system for years and possibly a lifetime. They will eventually get psychotherapy but the 6 to 12 sessions they are offered may not be enough to even begin to tackle the issues which have become so entrenched over the years. Mental health teams will have overworked and overstretched social workers and occupational therapists to help with issues around accommodation, employment, and social engagement which may be compounding problems. But while the person waits patiently on a housing list for many years, they will still be left to deal with the demons in their heads. A solution to this all-too-common problem is desperately needed.

Thankfully, these people are finally now being offered access to clinical trials for treatment with psychedelic assisted therapy. And so far the results have been very promising.



Psychedelic assisted therapy is being shown to be effective as a treatment for Treatment Resistant Depression, OCD, PTSD, Addiction, and Eating Disorders, among others. Most of these trials are Phase 2 with some now in Phase 3, meaning more evidence needs to be gathered before psychdelic assisted therapy is deemed an effective treatment that can be rolled out publicly on a large scale. With current trajectories, MDMA will likely be medically licensed next year, and Psilocybin the year after.



So what is the difference between Psychedelic medicines and SSRI's?

Serotonin is an important neurotransmitter when examining this question as both medicines act on serotonin receptors. The difference is which serotonin receptor they act upon. Classical psychedelics are Serotonin 2A receptor agonists, while SSRI's primarily act on Serotonin 1A receptors. SSRI's also activate other serotonin receptors which are responsible for their side effects. Activation of Serotonin 2c receptors can cause sexual dysfunction while activation of Serotonin 3 receptors cause nausea, diarrhoea, and muscle cramps.



SSRI's also exert some effects on Noradrenaline in the amygdala which reduces anxiety but also causes emotional blunting. They may also cause a reduction of Dopamine in the frontal lobes, leading to further emotional blunting. Recent studies have shown that chronic escitalopram reduced reinforcement sensitivity compared to placebo. This explains the common complaint that SSRI users have that, although they are glad that their depressive and anxiety symptoms are less severe, they also feel numb and find it difficult to feel truly happy or enjoy things as fully as they used to.




'It did help. It cut the bottom off the peaks and troughs which helped me cope. It didn’t solve anything, but it helped me manage in the day to day. Some people might argue that’s all you’d want but it wasn’t really dealing with the issue underlying the problem.'


'Medications just suppress, it never feels like it’s making a change.'


'It’s like taking a painkiller for a toothache, you don’t get to the source of the problem.'


'I get depressed, I go on the pills, they eventually work partially, then I try to come off them. I’m ok for 6 months, then it comes back, that’s been the pattern.'


'I tried it must be 15 different medications over the years, many caused weight gain, which I’ve never gotten off, and all of them made me sleep all the time.'



The same patients were asked about their experiences after taking Psilocybin:


'It’s almost as if when you take the capsules it’s like taking onboard your own psychotherapist.'


'I saw negative patterns in my life where if something bad happens, I used to just put it to the back of my mind. Afterwards, I allowed myself to experience everything - even if it is sadness. Now I know how to deal with my feelings rather than repress them.'


'The dose helped me realise why I felt the pain in my chest, I saw it visually and felt it emotionally, then I felt so much lighter, like something had been released. It was an emotional purging, the weight and anxiety and depression had been lifted.'



Psychedelic medicines' effects on Serotonin 2A receptors are completely different. Instead of causing emotional blunting, they cause increased emotional sensitivity for 4-8 hours after ingestion. If mediated properly (e.g. with appropriate psychological support and positive environmental conditions) this acute neuroplastic state can be used to facilitate learning, insights, reframing of problems, and eventual acceptance with potentially enduring beneficial effects. Moreover, there is reduced anxiety and improved general well-being during the post-acute ‘after glow’ of a psychedelic experience related to agonist-induced Serotonin 2A receptor downregulation. The quality of a psychedelic experience is known to be highly sensitive to the 'set and setting' in which it occurs and to be consequently predictive of long-term mental health outcomes. Significant therapeutic work can be done during this window of increased sensitivity and openness if the right therapeutic setting is provided.

A key function of brain serotonin transmission is to engage processes necessary for change, when change is necessary. SSRI's remain a very useful drug for relieving symptoms of depression and anxiety, but it is psychedelic medicines, not SSRI's, that will allow meaningful change to happen. Using medications to facilitate change rather than to benumb is an entirely different way of working in the mental health sector. Embracing this paradigm shift will require a change to the entire system of how mental health treatments are delivered. Specialised teams with designated clinics dedicated to psychedelic assisted therapy will be needed, with treatment protocols emphasising the importance of the therapeutic journey from preparatory sessions pre-dose, to comfortable and natural settings during the dose, on to comprehensive integration sessions post-dose. It is time for us now to engage in theses processes of change as, for the countless number of Irish patients with treatment resistant disorders, change is absolutely necessary.







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1 Comment


Pat Dee
Pat Dee
Jul 20, 2023

Super delighted to have found this site, what a breath of fresh air, to see the new face of healing shine through. I never thought I'd live to see the day of such change here in Ireland. Holistic healing taking place in it's true sense.

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