Beyond Blue Mondays: The Problem of Post-Psychedelic Depression

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The day after a psychedelic trip is often described in two very different ways. For some, there’s the “afterglow”: a lingering sense of joy and clarity that can last days or even weeks. But there’s also a lesser-acknowledged counterpart: the psychedelic hangover, which may accompany an afterglow in some mitigated form. This can mean feeling drained, irritable, foggy, or emotionally flat in the hours or days after a session. 

Psychedelic drugs are being widely explored for their potential to treat depression. It is well-recognised that MDMA, better-known as ecstasy, can create severe crashes and comedowns (Blue Mondays and Suicide Tuesdays) that evolve into mood disorders – yet little investigation exists on equivalent risks among classic psychedelics. 

The Post-Psychedelic Plunge

A survey of over 600 psychedelic users found that 6.7% reported experiencing thoughts of hurting themselves or others lasting beyond the day of the experience. Clinical trials have also documented cases of emergent suicidality: one analysis noted that about 7% of MDMA or psilocybin therapy participants reported some increased suicidal thoughts or self-harm.

Early surveys of adverse reactions to LSD in the 1960s noted that lasting psychosis (schizophrenia-like states) was a primary concern, whereas purely depressive states were considered rare. In the 1960s and 1970s, these states were reportedly known as an ‘Acid Funk’. By 1985, some clinicians acknowledged occasional depressive or manic episodes triggered by psychedelics. Recent research indicates that affective disorders (mood disorders) may in fact be a significant portion of psychedelic complications. A 2024 systematic review of published case reports found 17 cases of major mood disorder following psychedelic use – 11 cases of depression, 3 of mania, and 3 involving episodes of both. 

One large study of 608 people with post-psychedelic difficulties found that LSD was among the substances associated with the longest-lasting struggles. LSD’s effects can last 6 to 12 hours, with a comedown period that may extend up to 24 hours. During this time, users may experience a hangover of fatigue and physical exhaustion, anxiety and agitation, low mood, and issues with sleeping. Research indicates classical psychedelics may promote structural neural growth (dendritogenesis, synaptogenesis) in brain areas tied to mood regulation. These “reset” effects can lift depression (though one controlled study found no change in peripheral BDNF levels). 

MDMA, meanwhile, causes a massive serotonin (and some dopamine) release by reversing the serotonin transporter, leading to acute euphoria and empathy. The terms “Blue Mondays” and “Suicide Tuesdays” refer to the depressive period typically occurring midweek, nominally on Tuesday, following weekend use, due to this serotonin depletion. Parrott (2002) notes that 80–90% of weekend ecstasy users report a “mid-week blues” or feeling down a few days after use. Abstinent heavy MDMA users often show persistently reduced serotonin markers and cognitive deficits consistent with depression-prone neurobiology.

Burnouts and Comedowns

LSD and psilocybin don’t deplete serotonin in the same way as MDMA, but they do cause downstream changes in neurocircuits that could affect mood once the drug wears off. For example, one study found that one month after psilocybin, amygdala responses to emotional stimuli had returned to baseline (after being reduced at 1 week). This suggests the brain’s emotional processing might initially be positively altered, then “reset” itself – potentially overshooting in some cases into a negative state. 

A Reddit user recalls feeling “great for a week” after a 6 g psilocybin trip, only to “crash hard” a week or two later. On Shroomery, one person describes a powerful psilocybin tea experience that left them feeling “dirty… empty” months on. Others write of fatigue so severe it disrupted otherwise stable lives, with one group of friends experiencing “debilitating tiredness” for more than a week after a shared psilocybin session. Similar patterns appear in ayahuasca accounts: one person said they felt like they were “recovering from surgery” for three weeks after two consecutive ceremonies; another reported being “EXHAUSTED” six days after the last trip, including a marked emotional dip.

Cognitive scientist Marta Kaczmarczyk notes that such outcomes may stem from nervous system overstimulation, which can trigger depersonalisation, hypomania, or burnout – particularly in those with “overactive dopamine systems” who are “hypervigilant, seeking a lot of stimulation,” and therefore at higher risk for post-psychedelic hypomania. There is speculation about hormonal factors (for instance, the role of cortisol or adrenal fatigue after intense psychedelic experiences) and inflammatory responses (some research hints at immune system changes post-psychedelic).

On psychedelic forums, it’s not hard to find posts titled “Depression after LSD”. For instance, a user on the Shroomery forum described being “overwhelmed with depression” in the days after an LSD trip. This individual had prior mild depression that seemed vastly exacerbated by the LSD episode. A more extreme LSD anecdote was shared by someone who had a traumatic bad trip at 17 and afterwards “felt dead inside” for months. They described 4 months of near-constant existential depression and confusion following the trip, eventually seeking therapy to recover. The Berlin Psychedelic Ambulance Clinic has noted that many patients seeking help had panic attacks on LSD or ayahuasca and then continued to experience panic afterwards. In such cases, the trip itself was a traumatic event, and the post-trip depression may be akin to a trauma response (feelings of fear, helplessness, and negativity about life following the ordeal).

Hallucinogen Persisting Perception Disorder (HPPD) cases sometimes include prolonged anxiety or depression. Among 29 published flashback cases, 8 had extended depression, some lasting years. Bremler et al. (2023) interviewed people with chronic negative outcomes from psychedelics and found ~80% re-experienced aspects of their distressing trip (“emotional flashbacks”). Nearly half reported persistent disconnection or derealisation after the experience. Someone who develops chronic HPPD may experience intermittent anxiety and low mood for several years as a consequence. 

Do Psychedelics Raise the Risk of Depression?

The epidemiological picture is mixed. Some large surveys suggest that classic psychedelics may be linked to better mental health outcomes. For example, an analysis of over 190,000 U.S. adults found lifetime use of LSD, psilocybin, or mescaline was associated with lower rates of recent psychological distress, suicidal thoughts, suicide planning, and attempts. Another survey of 135,000 adults found no overall link to suicidality, but among people who had depression before age 18, psychedelic use was tied to fewer suicidal thoughts and plans. 

Other studies tell a different story. A CDC survey of 125,000 U.S. high school students found that psychedelic users were more likely to feel sad or hopeless, think about suicide, and make suicide plans. More recent data from 240,000 adults (2015–2020) showed that past-year LSD users were more likely to report depression and suicidal thoughts, salvia users were more likely to report suicidal thoughts, and DMT/AMT/Foxy users were more likely to have made suicide plans. In the same dataset, ecstasy users had lower rates of distress, depression, and suicidal thoughts, which raises questions about whether its associations are explaining real patterns.

That said, all of these surveys have a major blind spot: they usually only include people well enough to take part – missing those who have died, are homeless, institutionalised, or too unwell to respond – so they may underestimate the most serious harms. They may also be subject to a novel sampling bias, being that depressed people are perhaps more motivated than ever to try psychedelics as a form of self-treatment. Unbiased evidence will therefore come from carefully-controlled longitudinal studies. 

Depression in the Clinic

It is highly likely that controlled environments enable a reduced risk of adverse events compared to population use, including depression and mood disorders. David Nutt claimed to Australian regulators that “no one has ever come out of psychedelic therapy more depressed”. In reality, several patients have emerged from recent trials with worsened suicidality. Müller et al. (2025) reported on a 60-year-old patient with treatment-resistant depression who died by suicide two days after psilocybin-assisted therapy. The patient had a history of delusional ideation, and the psilocybin session appeared to trigger extreme emotional dysregulation in the aftermath. 

Young and old age, prior mental illness (especially anxiety, depression, or psychosis), and poor coping skills predispose to harm. A detailed case report described a 71-year-old psychologist (“Dr.  A”) who engaged in an underground facilitator training programme involving six weekend psilocybin retreats over six months. Decades earlier, in the 1960s, she had stopped using LSD after experiencing an “existential crisis”. Four months after her final retreat, she was hospitalised with profound and persistent symptoms, including severe anhedonia, along with anxiety, insomnia, depressed mood, hopelessness, and passive suicidal ideation.

One striking story reposted on Shroomery (originally from Reddit, titled “LSD ruined my life”) was written by a user who took only ~50 µg of LSD as a teenager and had a drug-induced psychosis. Even though the acute trip itself “was pretty good,” in the following days, he developed delusional beliefs and had to be hospitalised. After the psychosis subsided, he was left with “crippling depression” and frequent suicidal ideations for months. He describes losing all joy and motivation: “For the next few months after my psychotic symptoms were gone I suffered from severe depression and suicidal ideations.” Eventually, about a year after the trip, at age 18, he attempted suicide. 

Higher doses correlate with more extreme experiences, which in turn correlate with a higher risk of adverse aftermath. In one study, most cases of long-term problems involved either an “excessively high dose” or very frequent use. One participant, for example, had taken ~500μg of LSD in one session (unknowingly) and had a massive psychological fallout. 

Existential Blues

Psychedelics can provoke profound existential and spiritual experiences, which can be uplifting or deeply unsettling. In surveys of users with lasting difficulties, the most common themes were anxiety/fear, existential struggle, and derealisation. For example, Evans et al. (2023) found that 42% of respondents described “existential/ontological difficulties” (17% explicitly “existential struggle”) after their experience. Feelings of meaninglessness, loss of purpose, or derealisation were frequently reported. In colloquial terms, some describe this as a “spiritual emergency”. These effects often persist: about one-third had problems lasting over a year. Interestingly, the study found that prior mental illness did not statistically predict who got long-term difficulties.

If unresolved, these thoughts can spiral into depressive symptoms. Among a sample of 608 users, 12% developed prolonged depression after their bad trip, and about 6% experienced suicidal ideation. One participant recounted, “I collapsed into a severe, almost catatonic depression…fell further into the abyss of hopelessness and despair… I did not see the point. This lasted over 2 months.”

In a COMPASS Pathways trial of psilocybin (25 mg) for treatment-resistant depression, one participant (pseudonym “Zakara”) experienced a worsening of suicidal ideation that persisted for weeks. By the day after her session, she felt her life was “pointless” and that her death was “inevitable,” with constant, intensified suicidal thoughts (though no immediate intent). Four days post-dose, her depression hit “the worst she’d ever felt,” including impulses to visit train tracks (a place she had ideated about). 

Another vivid account comes from a middle-aged Reddit user who took psilocybin mushrooms and experienced a nightmare trip. They described being “in a bright white space with ribbons of rotting flesh encircling me,” feeling utterly alone, convinced they might be “on another planet with no hope of returning home or seeing loved ones ever again.” This harrowing psychedelic vision of decay and isolation left a deep imprint. “Ever since then I have had anxiety with physical aches and pains and heavy depression about my own mortality,” they wrote. Prior to this, they said they were “never really been concerned about my own death” and had no history of anxiety or depression. 

An Erowid report titled “Existential Crisis and Unwanted Ego Loss” (by user standsure, 2019) details a difficult LSD trip that led to profound nihilism. The user took three hits on a whim and was caught in rumination of “the force of ‘human conquest,’ strangling every last living beauty from this earth”, saying that they “contemplated suicide matter-of-factly (absent of terror and anxiety), while at other points [they were] seeing a divine eye and matrix overlooking me.”

“I realised that no matter what I did, there was no way to escape being a firm member of a destructive civilization. The notion that an environmentally destructive civilization is the ‘natural evolution of humankind’ became imprinted on my cosmic view.”

It is worth examining other psychedelic and related drugs. One ketamine clinic warns that “occasionally people experience a worsening of depressive symptoms and suicidality which persists for up to two weeks after taking ketamine”. Such reactions may be related to the mind-altering nature of the ketamine trance. If the patient is unprepared, this can feel like an “existential assault”. For instance, in a first-person account in The Washington Post, a patient described her initial ketamine session as “vacillating between existential dread and crippling anxiety” as buried emotions surfaced. 

Classical ayahuasca research often emphasises its potential antidepressant effects. But large-scale data reveal that adverse mood reactions are not uncommon in the integration period. The Global Ayahuasca Survey (Bouso et al. 2022) collected data from over 10,000 ceremony participants worldwide. Strikingly, 55.9% of respondents reported some adverse mental health effects in the weeks or months after drinking ayahuasca. These were usually described as temporary depression, anxiety, confusion, or emotional turbulence during post-ceremony integration. Most (≈88%) of users interpreted these difficulties as “part of a positive growth or integration process” rather than a purely harmful effect. Still, 12% felt the need to seek professional help for their post-ayahuasca mental struggles. 

The Hope of Post-Traumatic Growth

Some emphasise that those who use psychedelics in a traditional community (e.g. with ongoing support from shamans or fellow participants) tend not to report long-term complications – or if they do, the community addresses it as part of the process. Conversely, those who use the drugs individually and keep their issues secret (out of shame or fear), or have no one who understands psychedelics, may remain stuck in confusion. The feeling of “I’m the only one who has ever felt this” can intensify the depression. 

One paradigmatic idea is that psychedelics induce a state of heightened neuroplasticity for some weeks after the experience. Fundamentally, this could be a double-edged sword. If the context is positive and supportive, the person may integrate positive changes (hence the lasting antidepressant effects seen in many clinical trials). But if the context or psychological setting is negative or unsafe, the heightened plasticity might encode negative patterns and dysphoria, leading to prolonged adverse effects. 

In the cases we’ve reviewed, common contributing factors were very high doses, challenging or “bad” trips, and difficult set/setting (e.g. chaotic environment, or internal distress at the time of tripping). Although the focus of this report is on crises and depressive outcomes, it should be noted that some individuals do find meaningful growth through the struggle. A global survey of ayahuasca users gives a reassuring note: despite 56% having short-term difficulties, most still considered the overall balance positive and kept attending ceremonies, with the negative outcomes integral to overall growth. The PLOS interview study reported that many participants, once they navigated their existential distress, emerged with improved mental health, self-development and psychological maturity. They often developed greater compassion and appreciation for life after coming out the other side.

Ed Prideaux | Community Blogger at Chemical Collective

Ed is one of our community bloggers here at Chemical Collective. If you’re interested in joining our blogging team and getting paid to write about subjects you’re passionate about, please reach out to Sam via email at samwoolfe@gmail.com