Psilocybe cubensis: a Practical Guide to Magic Mushrooms

An 18-part guide to better understand Psilocybe cubensis and the efficacy of a magic mushroom trip, with a neuroscience twist.

Brief History of Psilocybin:

For thousands of years, psilocybin-containing mushrooms were used in ritual and ceremonial practices. In addition, the Stoned Ape theory by Dennis McKenna suggests Homo sapiens evolved as a result of ingesting psilocybin-containing mushrooms. Psilocybin and psilocin were first isolated by Albert Hofmann, a Swiss chemist, in 1957 and were first synthesized and sold as ‘Indocybin’ for clinical research by Sandoz Pharmaceuticals in 1958 [1].

Serotonin Receptors (5-HT):

Psilocybin mushrooms act by binding and activating serotonin receptors: a serotonergic hallucinogenic, a classic psychedelic. The psychoactive hallucinogenic effects are thought to be a response to the binding of psilocybin metabolites to serotonin receptors.

There are numerous serotonin receptors in which psilocin is an agonist (e.g., 5-HT2A, 5-HT2C, and 5-HT1A). Many factors influence the binding affinity and potency, such as mushroom type/ strain, fresh or dried mushrooms, and how the mushrooms were stored or preserved. The ratios at which binding occurs may also influence the trip’s psychoactive effects and intensity. The activation of 5-HT2A, a main excitatory receptor, is thought to underlie hallucinations [2].

More research is needed to understand the effects of psilocybin coupled with other substances. Especially as psilocybin is to be used during clinical treatment, many individuals looking for a new treatment may already be on long-term pharmaceutical interventions (i.e., SSRIs).

Selective serotonin reuptake inhibitors (SSRIs) work on serotonin receptors. These are your ‘prams and ines’ (citalopram, escitalopram, fluoxetine, paroxetine, and sertraline). The efficacy of SSRIs (like most drugs) is highly debatable. Taking psilocybin while taking SSRIs or other psychostimulants may have adverse effects [3].

Psilocybin, psilocin, and other tryptamines relationship & pharmacology:

Psilocybin is an indole-alkylamine (tryptamine) compound found in mushrooms. Psilocybin is a pro-drug that rapidly metabolizes (i.e., breaks down) into psilocin following ingestion [5].

Current literature suggests psilocybin cannot pass the blood-brain barrier (at least not efficiently), but its metabolite psilocin can, which results in its psychoactive effects. Both psilocybin and psilocin are tryptophan-based indole alkaloids. Following ingestion of psilocybin mushrooms, the psilocybin is converted into psilocin which has a high binding affinity for 5-HT2A receptors.

There are additional tryptamines found in psilocybin mushrooms (e.g., Baeocystin), and these metabolize into other compounds, respectively (e.g., norbaeocystin). To date, it is unknown which specific compounds and ratios of 5-HT activation result in the psychoactive hallucinogenic effect produced by magic mushrooms. Psilocin is expected to produce the trippy effect, although more research is needed into the other compounds found in natural psilocybe species.

Brain Regions Involved with Psilocybin Use:

Psilocin primarily affects the prefrontal cortex (PFC), which sends and receives projections from numerous brain regions, each region demonstrating unique functions. Animal research using neuroelectrophysiology recordings allows more insight into which brain regions and neurotransmitter types are affected to understand better the effects of psilocybin on the brain and behavior. Additionally, research suggests psilocybin use modulates serotonin expression across the brain. The list of brain regions affected by psilocybin will grow with new scientific discoveries.

Serotonin (5-HT), the gut, and psilocybin:

In addition to 5-HT in the brain, the gut derives most of the serotonin in the body. It is an important gastrointestinal signaling molecule [7]. There are some reports of nausea and vomiting following psilocybin ingestion. More research is needed to understand better the gut-brain axis and the effects of serotonin modulation.

I hypothesize, due in part to the activation of serotonin receptors by psilocybin, 5-HT in the gut signals to the central nervous system, and this regulates digestive reflexes such as nausea. Serotonin receptor activation may cause gastrointestinal upset.

Is it legal to grow, use or sell psilocybin containing mushrooms in the USA?:

In the United States, psilocybin mushrooms and psilocin are classified as Schedule I drugs under the Controlled Substance Act. In short, this means the United States government has deemed psilocybin and psilocin to have no medical benefits and have a high potential for abuse. Therefore, as of now, any use, possession, or sale of psilocybin is federally illegal.

As of 2020, Oregon passed Ballot Measure 109 to decriminalize possession of psilocybin and legalize the use of psilocybin in therapeutic settings. Following Oregon, several municipalities across California (Oakland and Santa Cruz), Washington (D.C.), Washington state, Massachusetts, Michigan, and Colorado (Denver) decriminalized psilocybin.

Legality of psilocybe spores:

In the majority of states (excluding California, Georgia, and Idaho), it is legal to possess psilocybe mushroom spores for research purposes only. Psilocybe cubensis spores do not contain (a significant amount) psilocybin [4]. Thus, it is legal to have psilocybe spores. However, it is illegal to cultivate spores into mushrooms that may contain psilocybin. Look into your local state and municipality laws for more legal information.

War on drugs or the war on us, the people?:

Wait for the discussion on the US government program MK Ultra and the war on the control of our minds. Drugs can be highly detrimental to your health. Consuming substances can have a long-lasting effect on your mental health. When serotonergic drugs with similarities to psilocybin, like LSD, have been studied for mind control, use extreme caution when messing with your psyche.

Rather than look into ourselves, maybe we need to look outside. Religion (i.e., relation with a higher power, not necessarily a religious group) can have just as profound, if not more profound, positive impact on lives than taking drugs. Likewise, habitual exercise and healthy living may negate the need or want to ingest substances. Turning to pharmaceuticals as a therapeutic for mental health should be more of a last resort.

Typical dosage for Psilocybe cubensis mushrooms:

Mushrooms lose about 90% of their weight when dried. Within psilocybe cubensis, there are many strains (e.g., Penis Envy, Albino A+, Golden Teacher, Colorado, Fiji, etc.), all with varying quantities of psilocybin, baeocystin, beta-carbolines, and likely other compounds yet to be studied.

If you’re planning a trip in your favorite rocket ship (your brain) a macrodose may do just the job. With a macrodose, individuals report various feelings, from anxiety to bliss to complete ego dissolution.

Individuals report feelings of ‘ego death or dissolution’ at high doses. Where oneself temporally becomes undifferentiable from the world or reality. Some people believe these feelings are necessary for the therapeutic benefits of psychedelics, while others suggest that the hallucinogenic effect is unnecessary.

Macrodoses are the dose that can have you bawling your eyes out and seeing what you have been hiding from yourself. That past trauma you thought you could ignore, cannot be ignored. These doses may help unveil what you’ve been suppressing. Cathartic, but you must know how to implement and understand your trip, or these doses can mess with your mind.

Not ready for the plunge but need a slight shake-up to the daily monotony? A microdose can be just the thing! The perfect state of flow; better and more productive than caffeine and marijuana. Low to no visual disturbances.

Some people view a microdose of psilocybin as a natural supplement. Yes, and supplements are still drugs. Typically, people implement microdoses into their weekly routine with a dose 3-4 times a week. These amounts can lead to more productivity and contentedness. However, as dosages are highly variable in mushrooms (and across strains), a little too much and you may get lost in the mind.

How long does a mushroom trip last?:

As discussed in previous sections, many variables affect a mushroom trip’s intensity and length. The set and setting, how much food is in your stomach, the rate of your metabolism, the type of mushrooms, etc.

A trip can be differentiated by two stages: acute versus chronic effects. Acute effects of psilocybin occur immediately following ingestion until the immediate effects wear off (< 8 hours). Chronic effects of psilocybin use can be observed for at least four weeks, with users reporting lasting feelings of content months of psilocybin use.

Importance of Set & Setting:

Timothy Leary and colleagues at Harvard popularized the importance of ‘set’ and ‘setting’ when it came to using psychedelic substances. The idea that the mindset needs to be ready for the mental journey while being in a comfortable environment. Imagine tripping in a small dingy city apartment or with a group of strangers versus being outside in nature with loved ones. A ‘bad trip’ is often the result of the mind and environment not being suitable or ready for a trip.

To Kill a Bad Trip:

What to do when a bad psychedelic trip comes to you. Relax and breathe, unless allergic, there have been no reported deaths due to the ingestion of Psilocybe cubensis. Sometimes psychedelic trips can be an emotional rollercoaster. If the feelings become too great, the best thing to do is to rest, talk with someone, and wait for the trip to end.

For some individuals, a dose of a benzodiazepine (benzos) will help take the edge off of a bad trip by triggering a release of GABA to sedate the system. Although they don’t block the serotonergic effects of psychedelics the release of GABA can offer some relief. Benzos are a class of highly addictive antidepressant – so dangerous withdrawal can be fatal.

Ketanserin, although not readily available, may provide relief to a bad trip. Ketanserin is a 5-HT2A antagonist, which may block the hallucinogenic effects of classic psychedelics [6]. Both in clinical and animal research, Ketanserin is used as a pre-treatment to block the effects of psilocybin [and other serotonergic hallucinogens (e.g., LSD)].  

Fresh vs. dried Mushrooms:

If you are reading this section, you may be fortunate enough to have the option of fresh (freshies) or dried psilocybin-containing mushrooms. However, with all mushrooms, the actual dosage of psilocybin/psilocin is highly variable across psilocybe species.

More research is needed to understand the pharmacological differences between fresh and dried psilocybe mushrooms. Suppose I was to report from personal experience (but I am not – pleading the 5th here!). In that case, there is something extra magical about ingesting fresh magic mushrooms with more visual disturbances produced than their dried counterparts. You have been gifted fresh psilocybin mushrooms; now what? Eat them as is, toss’em in a salad for a low-carb option, throw’em on a slice of pizza, or compost’em because drugs can be harmful — your options are endless.

If the timing for consumption is off, do not fret. You can store the freshies in a brown bag in the refrigerator for 1-2 weeks. Use a brown bag rather than a plastic bag or container, as the mushies need to breathe just like us, and this will prevent soggy mushrooms.

Another option is to dry the mushrooms, preferably with a dehydrator or your oven set to an extremely low temperature for an extended amount of time. Once dried (and stored ‘correctly’), the mushrooms will last years. From this point, you can eat the dried mushrooms and enjoy their woodsy flavor or take them one step further. If I was to have a favorite option outside of freshies (but I do not — pleading the 5th again), drying the mushies and grinding them to be capsuled is a convenient way to measure weights for microdoses. To ensure your mushies stay potent and dry, add a few desiccant packets to a glass air tight container and store in a dark cool environment.

Blue Honey:

See the Fun Fungi Fact below for why we call it Blue Honey! Honey, is an antimicrobial compound, and has been used as a preservative (and medicinal substance) for thousands of years.

To preserve psilocybe cubensis, add dried ground mushrooms (ensure they are bone dry — absolutely no moisture) to a glass jar of honey. Blue honey is the perfect concoction for your favorite warm beverage or drizzled on top of your favorite snack. Delicious! Whoever said mushrooms don’t taste good has yet to have them prepared ‘right’.

Psilocybin as a treatment vs. ‘just getting high’: Abuse potential

Therapeutic potential or a recreational drug. Can both be true ─ and beneficial?

The majority of research on psilocybin has been conducted on healthy participants or in animals. Research is restricted to behavioral models that only sometimes translate to efficacious use. However, more studies are emerging where psilocybin is used to treat psychiatric disorders and cluster headaches [8, 9].

List of disorders psilocybin being investigated to treat:

• Major depressive disorder (MDD)
• Treatment-resistant depression (TRD)
• Generalized anxiety disorder (GAD)
• Post traumatic stress disorder (PTSD)
• Alcohol use disorder (AUD)
• Substance use disorder (SUD)
• Cluster headache

There is a big difference between wanting to try psilocybin as a therapeutic for a disorder and getting a little trippy. It is like breaking a bone and getting a prescription for hydrocodone to treat pain versus buying a pill from the homie for x,y, or z reasons. Drugs can act as medicines and be good, but drugs can also be straight-up bad and fill your life with toxicity. Although just because you do not have a diagnosis from a doctor does not mean psilocybin cannot be helpful. Be honest with yourself and why you are choosing to take psilocybin.

Mushrooms & Marijuana:

Marijuana is known to induce anxiety in some users. Unless you are an experienced marijuana user (a cannabis connoisseur or THC gremlin), combining psilocybin and marijuana may be overly stimulating. Even for the green ganja lover, too much marijuana may lead to a bad─ overwhelming trip.

Psilocybin & MDMA: Hippie-Flip

Word on the street is [some] people enjoy partaking in a combination of psilocybin + MDMA (aka Hippie-flip). I hypothesize that MDMA reduces the anxiety produced by psilocybin.

Ingestion of MDMA results in increased serotonin release, while psilocybin works by activating serotonin receptors. Coupling the two substances overwhelms the brain with serotonin and the activation of serotonin receptors. The anxiety reduction, coupled with the positive feelings produced by MDMA, results in a supposedly pleasant experience. When psilocybin can make you feel stuck in your head, maybe the addition of MDMA releases those stuck feelings to get outside of your head.

It is all about taking the ‘right dose’ at the ‘right time’ in the ‘right place’. The go-to dose reported for this mix is between 1 – 3 grams of psilocybin ingested 1 – 2 hours before a dose of 50 – 100 mg of MDMA. Unlike psilocybin, MDMA is a riskier drug that can be dangerous and deadly. Use extreme caution when engaging with molly; she’s known to lead to trouble and depression when abused.

To minimize some danger when taking MDMA, test (all crystal-powdered-pill) substances with a drug reagent test kit. Reliable test kits can be found on DanceSafe, where they make specific kits for testing MDMA and all other substances.

Fun Fungi Fact: Why do mushrooms turn blue?

Psilocybin containing mushrooms turn blue when injured due to the degradation of psilocybin [10].

My Opinionated Going Forward:

Synthetic analogs of psilocybin are being produced (e.g., psilacetin). Rather than take several months to grow and extract the psilocybin from mushrooms, a synthetic version can be produced, which is also more cost-effective. However, as the modulation of serotonin and the varying binding affinities of 5-HT differ, the efficacy of synthetics or psilacetin versus psilocybin continuing fungi must be researched further.

Synthetic psilocybin will take over the market as it becomes cheaper to produce. Companies will put less of a focus on treatment and more of a focus on profits– as the usual. Hence the psychedelic drug market is expected to reach over $ 8.31 billion by 2028, as reported by InsightAce Analytic in Bloomberg [11].

Using psilocybin can significantly impact your mental health- for the best or the absolute worst. When you thought your psyche was already in shambles, wait till a ‘bad trip’ for you to really feel destroyed and worthless. On the contrary, psilocybin may be just the thing to pull you out of your weird funk. Use caution with anything ingested: food, drugs, media, vaccines, etc.

Using substances is not necessary for finding substance in your life. Please reach out to those around you if you are struggling with your mental health. Finding community and support can often do much more than drugs will ever do to make you feel better about yourself.

This guide is not meant to condemn or condone the use of substances but rather provide an informational overview. If you see any inaccuracies or would like to make a suggestion, please reach out!

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