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How Psychedelic-Assisted Therapy Can Help Treat Depression

Psychedelic-assisted therapy is emerging as a novel treatment for many disorders, both psychological and somatic. Most notably, studies on these medicines have targeted their efficacy in treating depression. Today, science has produced ample findings that support the significant impact that psychedelics have on treatment-resistant depression.

Today we’ll be discussing how psychedelic-assisted therapy can help treat depression from a neurological and subjective perspective. We’ll be using the most up-to-date studies to analyze the impact that psychedelics could have on depression. We’ll also review exactly how psychedelics can be used to treat depression, at home.

The Neurological Benefits of Psychedelics on Depression

From a neurological perspective, many studies have found psychedelics to be an incredibly effective therapy for treatment-resistant depression. A 2018 study led by Fei-Fei Zhang and colleagues found that the prefrontal cortex of people with depression experiences significantly abnormal hyperactivity. 

This brain region is responsible for moderating social behaviors, the way we express our personality, our inhibitory control, thought-related patterns, and memory. They also found significant deformities of the bilateral putamen and left thalamus, with reductions in the orbitofrontal prefrontal circuit (OFC). The OFC consists of the posterior cingulate cortex (PCC). 

The angular gyrus, a region of the default-mode network (DMN), was found to experience overactivity. This overactivity contributes to increased rumination and heightened suicidal behaviors. Other brain regions found to experience abnormal activity and shape were the anterior cingulate cortex (ACC), the temporal gyrus, and the superior frontal gyrus.

In a 2011 study conducted by Robin L. Carhart-Harris et al., functional magnetic resonance imaging (fMRI) was used to study the effects of psilocybin on 15 volunteers. They found a significant reduction in cerebral blood flow to the medial prefrontal cortex (mPFC), bilateral thalamus, putamen, the posterior cingulate cortex, bilateral angular gyrus, orbitofrontal cortex, and middle and inferior frontal gyrus.

To understand how these psilocybin-induced modulations subjectively affected the participants, researchers compared their CBF changes to each participants’ ratings of drug effects and intensity. They found a significant increase in functional connectivity within the mPFC, compared to no changes in the placebo subjects.

They also found a significant decrease in activity within the default mode network (DMN). The DMN is activated in absence of our focused attention, during self-referencing when we’re daydreaming of the past or ruminating about the future. Hyperactivity of the DMN thus increases negative rumination, and these studies support the theory that DMN-induced hyper rumination could be ameliorated by psilocybin. 

Because pessimism is a defining characteristic of depression, a 2006 study, amongst others, was led by Zubin Bhagwagar and colleagues, to find its neural correlates. Results confirmed a significant link between trait pessimism and a reduction of 5-HT2A (serotonin) receptor activation.

Luckily, LSD, DMT, and psilocybin are psychedelics that bind to 5-HT2A receptor sites and stimulate their signaling. A 2019 study by Clinton E. Canal discusses how this stimulation increases phosphoinositide hydrolysis, which stimulates the production of inositol phosphate, and this activates protein kinase C (PKC).

A 2021 study conducted by Ghanshyam N Pandey and colleagues found that adults who experience depression and suicidal ideations demonstarted significant decreases in mRNA expression of PKC. This allows us to conclude that serotonergic psychedelics can help modulate depression symptoms by activating PKC signaling.

A 2001 study by Robert M. Sapolsky found that people with depression experience significant shrinkage of the hippocampus (the brain’s memory center) due to reduced cell proliferation (cell division and growth). 

A 2016 study by Briony J. Catlow and colleagues found that psychedelics stimulate hippocampal neurogenesis (the birth of new neurons). This neurogenesis activates the formations of synaptic connections for overall enhancement of episodic memory function and  the replacement of dead or damaged neurons. 

Clinical Trial Findings on Psychedelics for Depression

In an effort to understand the real-life impacts of psychedelics on people with depression, we look to the results of recent clinical trials. In a 2008 follow-up study, researchers investigated the duration of benefits in 36 participants 36 who had taken oral psilocybin. 

The study found that after 14 months, 67% of participants rated the psychedelic experiences as being one of the five most meaningful and spiritual life experiences. 64% of the participants reported a sustained increase in life satisfaction and well being, 14 months post-psychedelic trip. 

In a 2011 study, researchers found a significant increase in psychological openness after one high dose of psilocybin. This significant increase was sustained at a one-year follow up. T-scores for openness in participants who had a complete mystical experience, increased an average of 6 points. 

A 2022 study conducted by Natalie Gukasyan and colleagues, tested the effects of two psilocybin doses with supportive psychotherapy on 24 patients with major depressive disorder. The GRID-Hamilton Depression rating scale was used to measure depression symptoms. 

The study found that 7 days after treatment, 71% of participants demonstrated at least a 50% reduction of GRID-HAMD scores, with 58% qualifying for complete remission. In a 12-month follow up, 75% of participants sustained their responses and 58% sustained their remission rate.

The mean scores of the Quick Inventory of Depressive Symptoms (QIDS) test found that 79% of participants experienced clinically significant reductions in depressive symptoms, and 54% were in remission. At the 12-month follow up, 79% sustained response rates and 67% maintained remission rates.

The Beck Depression Inventory II (BDI-II) test showed a clinically significant reduction in depression symptoms in 79% of participants, with 67% being in remission. After 12 months, 83% BDI-II scores showed that 83% sustained their response and 75% were still in remission.

The Subjective Benefits of a Psychedelic Experience  

By now, we’ve come to a good understanding on the neurological benefits of a psychedelic experience. Next, we’ll explore how the subjective experience of a psychedelic journey can help reduce depressive symptoms. To illustrate this, let’s paint a comprehensive mental picture.

You’re born. An aerial shot of your mind projects the image of an almost untouched prairie of grass. This prairie represents all of the neurological action potential our brain has yet to experience. As you grow older, this prairie becomes carved with paths that represent thought patterns and routines, while other slithers of grass still remain untouched. Why is that? 

What gave way for those specific patterns? And more broadly, what was the deciding force behind the precise trajectories of our mental prairie paths? At its core, we’re discussing the influence of social conditioning on the pursuits of interest in our lives, such as career choices, religious beliefs, and even our “type” regarding romantic relationships. 

Social conditioning is the behavioral effect of our nurturing and of environments. The physical habits and emotional patterns instilled in us, either directly or indirectly, by observation of our familial relationships, often create rigid belief systems by which we subconsciously and unconsciously steer our decisions.

Overtime, we come to view these belief systems as our own, as the foundations of our personality. However, this is where unhealthy coping mechanisms begin to plant seeds across our lives. For example, you may have been raised in a household where you consistently observed your mother being physically abused at the hands of your father. 

Unfortunately, your mother would incessantly complain to you about her broken marriage and the disrespectful behavior of your father. Still, your father never came home to an empty plate and your mother would beg him to stay after he’d return from his multi-day drinking binges

Now, as an adult, your conditioning may have carved very specific patterns into your mental prairie of grass. Many of the paths may lead to the same negative and intrusive mental and physical territories because they were paved by unhealthy coping mechanisms that were conditioned into you. 

In this example, such coping mechanisms could include codependency cued by fears of abandonment or drinking to numb internal conflict. Because your mother over shared her turmoils, you may isolate yourself and find it difficult to be vulnerable. All of these traits carve mental paths that when observed more broadly, have influenced the mental narratives that create our personality and thus our mental trajectories.

In a psychedelic journey, we’re offered the opportunity to experience life without the influence of our conditioning. Because activity is reduced in the default mode network, we’re able to observe ourselves from new perspectives, without the pervading filters of trauma

This relinquishing of rigid mental patterns very literally creates new neural pathways that are sustained after a psychedelic trip due to the formation of new neurons and the strengthening of neural connections. Thus, to circle back to our mental illustration, a psychedelic experience allows us to carve new paths in that prairie, to explore new trajectories that are uninfluenced by inauthentic expressions of the self. 

How To Use Psychedelics To Treat Depression

There are several ways to use psychedelics to treat depression, however the most important factor is receiving adequate preparation and integration support. In the studies we reviewed today, the significant reduction of depression symptoms were concluded after the participants went through preparation and integration sessions.

The sustainability of changes had a direct correlation to the amount of effort and attention they directed toward integrating the psychedelic experiences into their daily lives. Without integration, it can be very easy to fall back on old ways of being because we don’t allow ourselves the proper space to process the experience and examine its meaning.

Other factors to consider are whether you want to embark on a high-dose psychedelic experience or if you want to adopt a microdosing protocol. You aren’t limited in your choices, in fact, many feel that a high dose experience is incredibly beneficial for catalyzing quick, large-scale change, and that following up with a microdosing protocol helps maintain and fortify those changes.

A high-dose therapeutic psychedelic experience can be fairly straightforward, however, it’s helpful to consider whether or not you want to journey with professional assistance. Professional guidance can be immensely helpful for helping us establish appropriate intentions, manage expectations, institute safety protocols, and for integrating the experience. 

If you choose to seek professional guidance, it’s important you have the support of a qualified psychedelic facilitator. You should always have full autonomy over the course of your treatment and remember, a qualified facilitator should always be someone who has journeyed with many psychedelic medicines and thus knows the ins and outs of these experiences.

Microdosing regimens can be more self-led because its effects are very sub perceptual. There are many proposed microdosing regimens. Arguably, the most popular one is the Fadiman protocol. In this protocol, you take the microdose one day, don’t take it for two days, then take it again on the fourth day. 

For example, if you take your first dose on a Monday, you take a break on Tuesday and Wednesday, then take your second dose on Thursday. You continue this by taking a break on Friday and Saturday, then taking a dose on Sunday, and so on. This protocol is effective at ensuring that our tolerance to the medicine doesn’t build up, so we can experience consistent results.

The dosage that’s effective for you will be specific to your physiology. Those who take SSRIs for example, may find that they need a larger dose to experience desired effects. Therefore, the best practice is to start at a dose of 0.1 grams of dried psilocybin mushrooms, then increasing by 0.05 grams each day until you reach your threshold. 

Supplementary practices to a microdosing protocol could include daily journaling, meditation, yoga, or anything that allows you to instill mindfulness and self reflection into your daily routine. For a complete handbook on microdosing, scroll up to the top of our page and download our free microdosing guide!

Explore What It’s Like To Feel Connected

As we’ve come to learn today, psychedelics can be a powerful tool for treating depression. However, they’re also very useful in aiding with symptoms of anxiety, OCD, and even ADHD. Whatever your reason for exploring these medicines, Psychedelic Passage is here to service your journey.

We’ve made it our mission to curate a network of the nation’s most experienced and therapeutically-equipped psychedelic facilitators, so you no longer have to guess who’s qualified and who isn’t. Our 5-week program offers preparation and integration sessions, and of course in-person support during your psychedelic experience.

If you’re interested in embarking on a psychedelic journey or would like to learn more about the process, we empower you to book a consultation with us. Of course, you can always reference our resources page for an extensive bibliotheca of information on all-things psychedelic. That’s all for today, friends. Safe journeying!

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At Psychedelic Passage, we offer professional 1-on-1 guidance and companionship on your journey of healing. We simply can't sit back and let Americans continue to sit in silent suffering trying to battle mental health issues within a broken health care system, all while knowing that effective alternatives exist. We stand for the sacred, at-home, ceremonial use of psychedelics for consciousness exploration, which we believe to be a fundamental human right.


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