Psilocybins & LSD
Psilocybin, the primary psychoactive compound in magic mushrooms, is a prodrug that is rapidly converted into psilocin in the body. Psilocin primarily exerts its effects by acting as a partial agonist at serotonin 5-HT₂A receptors, leading to altered perception, cognitive shifts, and profound changes in consciousness. The activation of these receptors enhances cortical glutamate release via pyramidal neurons in the prefrontal cortex, resulting in increased neural plasticity, altered sensory integration, and a breakdown of default mode network (DMN) activity. These neurobiological changes contribute to the characteristic psychedelic effects of psilocybin, including visual distortions, ego dissolution, and altered time perception. Due to its relatively short half-life, psilocybin’s effects typically last 4–6 hours.
LSD (lysergic acid diethylamide) is a potent serotonergic psychedelic with a broader and more complex receptor profile. It functions primarily as a partial agonist at 5-HT₂A receptors, similar to psilocin, but also interacts with dopamine D₂ receptors and other serotonergic subtypes such as 5-HT₁A and 5-HT₆. This broader receptor activity contributes to LSD’s unique effects, which include vivid visual hallucinations, enhanced associative thinking, and prolonged perceptual alterations lasting up to 12 hours. LSD’s pharmacokinetics differ significantly from psilocybin, as it binds with exceptionally high affinity to serotonin receptors, prolonging its psychoactive effects. This high receptor affinity also accounts for the prolonged afterglow and lingering perceptual changes some users experience after an LSD session.
Combining psilocybin and LSD results in a synergistic amplification of serotonergic activity, leading to an intensified psychedelic experience. Since both substances primarily target 5-HT₂A receptors, their concurrent use increases cortical excitability and disrupts DMN function to a greater extent than either substance alone.
Subjectively, users report deeper introspection, intensified visual distortions, and enhanced emotional resonance. However, this combination may also increase the risk of challenging psychological effects such as overwhelming ego dissolution, anxiety, or thought loops due to excessive serotonergic stimulation. The duration of the experience is likely extended closer to LSD’s timeframe, with psilocybin enhancing the onset and peak intensity.
Scientific research on the co-administration of psilocybin and LSD remains limited, as most psychedelic studies focus on their individual effects. However, anecdotal evidence suggests that while the combination does not introduce fundamentally new pharmacological mechanisms, it can amplify the depth and complexity of the psychedelic state.
Theoretical concerns regarding serotonin syndrome are minimal at typical psychedelic doses, as both substances act primarily on receptor sites rather than increasing serotonin release.
Nonetheless, the psychological intensity of this combination warrants caution, particularly for individuals prone to anxiety, psychosis, or dissociative states.
Further research is needed to determine whether the combined use of these psychedelics enhances neuroplasticity or therapeutic outcomes beyond what is observed with single-substance administration.
This combination requires a lot of experience with substances separately, compliance with minimum dosages, rare repetition and a meaningful approach.
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