4-HO-MET

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4-HO-MET is a tryptamine psychedelic that has been minimally researched and is primarily sold through the research chemical (RC) and novel psychoactive substance (NPS) market. However, it does have a longer history of use than a lot of RCs, having been subjectively described by the chemist Alexander Shulgin in the 1990s and somewhat widely used since the 2000s.

It is known for producing less mentally intense, though highly visual experiences relative to psychedelics like LSD, psilocin, and 4-AcO-DMT. That is a fair general characterization of the drug, but its tendency to be recreational and clearheaded should not be overstated. Some users experience strong mental effects at common doses and for a large portion of users it will eventually become intense if high enough doses are used. As is true for essentially all psychedelics, it deserves respect and should not be treated as a risk-free substance. A proper set and setting remain important factors for reducing the risks and enhancing the positive aspects of the drug.


4-HO-MET = 4-hydroxy-N-methyl-N-ethyltryptamine ; metocin

PubChem: 21786582

Molecular formula: C13H18N2O

Molecular weight: 218.29 g/mol

IUPAC: 3-[2-[ethyl(methyl)amino]ethyl]-1H-indol-4-ol


TDC Documents

Experience Reports and Effects Analysis: Link

Effects Tally (Raw Data and Charts): Link (Note: Download and view for proper formatting.)


ROAs and Dose

Oral is the most common route of administration, followed by intranasal, and occasionally it is taken rectally or via injection (IV or IM). Because substantially more people have taken it orally than through other routes, more is known about the appropriate oral dose and usually that ROA provides reliable effects. Rectal administration is normally reported to work fine, but since it can be more of a hassle and does not offer a substantial potency difference, along with unreliably reducing nausea, it may not be worthwhile.

Intranasal use may cause temporary pain, though few reports have commented on that aspect of the administration. It also offers minimal potency benefit overall, but its faster onset is enjoyed by some.

There is a significant degree of inconsistency between users as to the drug’s potency, specifically the potency of its mental effects. Some users experience notable mental changes at common doses, yet others can use much higher doses with seemingly little risk of difficult experiences, though even if you are experiencing very manageable effects at higher doses, it is important to remain cautious since that quality of the drug may one day change.

Redoses

It appears to be more easily redosed than a lot of psychedelics. As a general rule, this practice is still discouraged because it adds an extra layer of unpredictability to the experience, but the reports tend to indicate it can bring back or increase the intensity while showing little evidence of acute tolerance and it has the benefit of extending the duration of a relatively short-acting drug. Some users report success taking 0.5 to 1x the original dose 1.5-2.5 hours after the first administration.

At strong+ doses this becomes progressively riskier. For example, it could mean a jump from 30 mg to 45-60 mg, rather than a more reasonable increase from 10 mg to 20 mg, so taking 0.5x or less for the redose is safer when working with higher amounts. Multiple redoses should be more strictly avoided.

Oral

Light: 5 – 10 mg

Common: 10 – 20 mg

Strong: 20 – 30+ mg

Most people use 10 to 30 mg. Among those who find the drug particularly easygoing, the reasonable dose range can extend into the 30s or 40s, but those does should not be taken by people who have not already experienced lower doses, and the dose should only be increased by a small amount each experience (e.g. 5 mg per use) instead of making large jumps.

Users who easily handle common to strong doses can still end up having difficult experiences upon pushing the dose higher. 4-HO-MET can be considered a more recreational psychedelic, but it is not boundlessly friendly.

Intranasal

Light: 5 – 10 mg

Common: 10 – 20 mg

Strong: 20 – 25 mg


Timeline

Oral

Total: 4 – 6 hours

Onset: 15 to 30 min

Although the duration is around 4 to 6 hours, the peak can be especially short at light to common doses, resulting in a substantial decline in the effects 3-4 hours into the experience, with more residual-level effects beyond that point. The duration is sometimes considered too short, but others find it nice to have a psychedelic whose strongest effects only stick around a couple hours, distinguishing it from drugs like LSD that use up the better part of a day.

The oral onset is faster than average. Occasionally people feel effects in<15 min, the most common onset time is 15 to 30 min, and most users feel it within 45 min. The earliest effects are normally bodily sensations, some anxiety, and a general sense that something is different, rather than visuals.

Anxiety, uncomfortable bodily effects, and a sense of being overwhelmed regularly occur during the comeup, with the experience becoming more comfortable as the effects progress. Sometimes the physical activation and GI effects kick in faster than the mood elevation and pleasurable aspects of the body high, but this uncomfortable period is brief and not everyone encounters it.

Intranasal

Total: 3 – 4 hours (The effects often decline within two hours.)

Onset: 5 to 15 min

Because it has a faster onset, intranasal use has a greater chance of being intense at the beginning, leading to more overwhelming and disorienting effects early on.

IV

Total: 1 – 2 hours

Onset: Within 5 minutes (Usually it has a near-immediate onset, developing into the core effects in a matter of minutes.)


Effects

Positive

  • Open eye visuals (OEVs)
  • Closed eye visuals (CEVs)
  • Easygoing headspace
  • Mood improvement and euphoria
  • Increased sense of humor
  • Laughter
  • Minimal anxiety
  • Music enhancement
  • Light to moderate entactogenic effects (e.g. increased appreciation and sense of connection)
  • Auditory hallucinations
  • Minimal bodyload
  • Increased sociability
  • Pleasurable body high (e.g. warm and/or tingling sensations)
  • Increased energy

Negative

  • GI distress (e.g. stomachache, nausea, indigestion)
  • Anxiety and panic
  • Confusion
  • Uncomfortable comeup or comedown
  • Paranoia
  • Cold sensations
  • Thought loops
  • Sweating
  • Sensation of overheating
  • Bodily heaviness (i.e. perception of your body being heavier)
  • Increased heart rate and blood pressure

Mental and Cognitive

Confusion and ‘Deepness’

Most often it has a fairly clearheaded mental state that almost feels like soberly experiencing perceptual and mood changes, or it causes transient periods of anxiety and confusion that are still more easily addressed by basic calming techniques and rational thinking than if you were experiencing high-dose LSD, psilocin, or 4-AcO-DMT, for example. It is relatively easy to distract oneself and a change of scenery, company, or music may be all it takes to address the more difficult periods of a common dose experience. Thinking can still speed up and thoughts frequently become more random and tangential, occasionally leading to thought loops and negative intrusive thoughts.

This same property of causing less thought alteration may reduce the chance of therapeutic benefit and insight, or it can simply produce less interesting mental changes, especially for someone familiar with mentally stronger psychedelics. The introspective and entactogenic qualities it does have are more likely to be focused on things like your life, habits, and relationships, rather than on classically “deep” spiritual and cosmic ideas, so in that sense it’s more grounded and more easily navigable because the mental state is closer to normal consciousness. A fairly common experience is feeling more connected to people in your life or to the world–for example, some people feel a profound sense of connection while in nature, but the majority of common dose experiences don’t include those effects.

Ego dissolution is a classic part of psychedelic experiences. Some beneficial or confusing experiences cause effects like not understanding who you are, no longer identifying with your feelings, not identifying with your body, and not remembering your name. This can be frightening, but it also carries the potential for insight since reducing the boundary between yourself and the rest of the world can mean not taking your normal patterns of thinking or your normal sense of self as seriously, helping to overcome rigid ways of being and self-centeredness. At typical doses significant ego dissolution is uncommon.

While it is fairly clearheaded, you should still expect it to be more difficult doing a lot of normal tasks, like answering the phone. Being unexpectedly confronted with those tasks has a good chance of provoking some anxiety and hesitation. You should not fool yourself into thinking you can handle everything just because you feel relatively normal. A lot of users do fine in calm settings, yet spiral into negative or difficult experiences if they try to do too much, like being in public and talking with strangers, partly because trying to hide that you’re on a drug can be very unpleasant on psychedelics. At the end of the day, you are still on a significantly altering drug, and anything that is unsafe when altered, like driving, should not be attempted.

Many users report feeling 4-HO-MET would be a good introductory psychedelic, giving people a way to understand what a somewhat trippy mindset is like and what psychedelic visual distortions entail while carrying comparatively little psychological risk. It’s been likened to 2C-C, 2C-B, and AL-LAD in this regard.

Anxiety and Paranoia

Particularly early on in the effects there can be anxiety centered around experiencing a change in your mental state and sensing reduced control over how you feel and what you perceive, which can leave people questioning their choice to have taken a drug and it can be a trigger for people to fight to maintain control, which is often counterproductive. These feelings normally do not make up a large part of the experience.

Concerns about physical and psychological safety may appear, and they are a common trigger of thought loops, but most people do not report a major issue with those thoughts. Because there is still a chance of anxiety and paranoia, it is good to have a trusted sober person with you since they can help alleviate irrational concerns.

A similar number of reports specifically mention no anxiety and even relaxed effects as those that mention some degree of anxiety or panic.

Mood

Normally it causes mood improvement and elation, with those effects appearing early in the experience. It can also feel life-affirming such that people are happy to be alive and happy to be having the experience. Psychedelics in general have an elating effect, but it is frequently covered up and distorted by anxiety and confusion, so the lower rate of those downsides with 4-HO-MET helps the mood elevation come across. It’s not entirely consistent with producing joyous experiences, but it appears more consistent than average. The general mood elevation is also often accompanied by a sense of freedom and a desire to explore, sometimes described as child-like curiosity.

Like with anxiety, periods of low mood can occur. As it is very much a psychedelic, those periods of low mood may come up spontaneously or be associated with an emotional response to difficult things in your life, and in that sense the low mood might not be entirely negative, but rather a trigger for personal growth.

Amusing

A very common effect is being more easily amused, as well as laughing for no reason. Some users end up laughing hysterically in an uncontrollable manner, though that effect is almost always positive. Similarly, smiling is a common effect, sometimes occurring without any laughter or amusement being present.

These properties exist with other psychedelics, but appear more common with 4-HO-MET.

Social

It is impairing enough to make communication more difficult and stressful, but socializing with people you trust can be more enjoyable. The drug can promote talkativeness and its pro-social effects tend to be brought out the most by calm environments and small groups, not large crowds.

Conversations may be more meaningful, producing some entactogen-like experiences.

Even if you are in the mood to socialize, it can be harder to communicate your thoughts. A lot of people report having essentially unimpaired, coherent thinking, but difficulty expressing their thoughts and feelings to others. You may also find yourself getting confused by the act of talking, in part because it can be harder to hold things in your working and short-term memory. Impaired communication is more common with higher doses.

Entities

A minority of users see or otherwise sense the presence of entities, with some qualitative similarities to entity experiences on psilocin or DMT. This almost exclusively occurs at strong+ doses and even using high amounts normally does not cause this effect. Normally the experiences are not frightening and the entities are described as seemingly benevolent, sometimes with the intent of helping the user.

In some of the experiences it seems the perception of entities may just be how users are perceiving a sense of detachment from an inner voice or the sense that there is a dialogue between two internal voices, such as a rational voice and an irrational voice.

Music enhancement

It is common to enjoy music more and to find songs more engaging than usual. Music also has a greater influence on your mood and thought processes, and some people find the songs they’re listening to partly sync up with the visuals.

Time Alteration

Most users do not experience a substantial change in the perception of time, but a notable minority report time dilation. Things can feel like they are taking much longer than they really are. Often this is a neutral effect, but it can contribute to negative experiences because people feel like they are stuck experiencing bad effects and despite rationally knowing they are on a short-acting drug, it does not feel that way.

Eroticism

A minority of users report an increase in sexual thoughts and imagery, but actual enhancement of sex has rarely been discussed and whatever effect is has on sex may not be reliably good, as is typically true for psychedelics.

Perceptual

Visual

Visual distortions are one of the most common effects and they will usually occur beginning at light doses, becoming very intense by strong+ doses. At common doses it causes open eye visuals (OEVs) and some closed eye visuals (CEVs). Rarely does it produce frank hallucinations, i.e. seeing things in the external environment that do not exist, but high doses can distort your perception enough as to nearly create novel items in your environment. High doses may also allow environments and scenarios to be witnessed with eyes closed, e.g. fanciful situations or scenes from your memory. Those internal hallucinatory experiences can feel a bit like a dream state.

It is known for its very colorful OEVs, which are normally fun to look at and which may be enjoyable enough to make up for an otherwise shallow experience. Surfaces breath and otherwise move, everything in your visual field can vibrate, boundaries between objects and the environment are reduced, and everything takes on a more lively appearance. Typically the visuals are bright, color saturation and intensity increase, and the colors can have a neon-like appearance. Geometric patterns are often seen and a number of reports specifically describe the visuals as Aztec or Mayan-like. Some users see scribbling in the shape of what appears to be letters, so it can seem like you are seeing words in an unknown language.

Usually it is worthwhile to look at nature or the sky rather than just viewing the inside of a building, though both experiences can be satisfying.

Facial features are frequently distorted in cartoony or otherwise unrealistic ways. For example, components of a person’s face can change size and hair may look a different color. Inanimate objects can also morph in a way that makes them look like faces, which is a common psychedelic effect. Seeing faces in objects can be unnerving, even frightening, but normally it is not. A lot of things that come off as somewhat creepy on 4-HO-MET are still relatively easily ignored, preventing the creepiness from triggering fear.

Heavy doses can cause visuals that are more immersive and a bit closer in their appearance to what is produced by DMT, but those effects are usually out of reach with normal doses. And the “breakthrough” dissociative quality of DMT is not really an element of 4-HO-MET, the visuals can just saturate your normal visual field.

After images are common, so moving an object or body part can produce a temporary trail of more transparent images across the movement path. The colors, patterns, fractals, etc may also stand out more when viewed in the dark, though your actual night vision is also likely to be impaired, so be cautious if you are trying to navigate in the dark. Viewing the CEVs or OEVs in the dark comes with a somewhat elevated risk of making the visuals more distressing and frightening.

Among the CEVs are colors, basic geometric patterns, and at the more intense end, complex fractals, but at common doses the CEVs are usually simple.

Despite not being mentally intense, it can be visual to the extent of being described as one of the most visual psychedelics. It is a bit unclear whether the intensity of the visuals is actually that unique or if the visuals simply receive more attention because the mental effects are comparatively tame. With other psychedelics the mental effects may be strong enough to make the visual component of the experience an afterthought.

The visual effects are not universal, but it is only a small minority of users who do not get substantial visual effects at common or strong doses. Though, for some people the distortions produced by lower doses are not very noticeable when you are not paying attention or when an object is moving, so focusing on still objects should make the visuals stand out more.

Auditory

It commonly distorts sounds, with effects like making things sound closer or farther, making them sound metallic, and changing voices such that they are perceived as slowed down or less human-like and generally weird.

Tactile

Tactile hallucinations are not a major aspect of the drug. Usually this effect just presents as making things you touch or wear feel a bit different, such as smoother or rougher. At high doses, a minority of people experience a sensation of bugs or other things moving on them or within their skin, but this is normally an element of psychotic experiences triggered by overdoses, so it is not something most people have to worry about.

Physical

The bodyload is relatively minor compared to many other psychedelics and the effects that exist are not always bothersome. GI issues like nausea are common, but the intensity of those effects is normally low. Vomiting is rare throughout the duration and nausea tends to be more present during the comeup.

Some of the other potential effects are muscle aches or tension (especially in the jaw, legs, and neck), sweating and cold sweats, shakiness and jitteriness, cold extremities (potentially from vasoconstriction), alternating between unpleasant sensations of hot and cold, and a sensation of your body being heavier. Heart rate and blood pressure likely increase moderately and users certainly perceive an increase in cardiovascular activity. A minority experience heart palpitations and chest tightness, but those are far more likely the result of stress than being from anything that could affect safety.

It can cause you to feel physically impaired, particularly when moving around. Some users report it is difficult to walk properly, with that aspect being compared to the effect of sedatives. A small portion of users get allergic or sick-like symptoms, sometimes exclusively during the comedown period. Those effects include a stuffy nose, itchiness, swelling, and skin rashes.

There are a handful of reports of users feeling like they need to urinate frequently, despite not actually needing to. This may merely be a sensation or there could be an effect on your ability to fully empty your bladder. For some users this sensation seems to be a manifestation of stress, so it can even go away during the experience if they calm down and reframe what they are dealing with.

While a bodyload may occur, it can also produce a body high, and the sensations experienced on the drug can often be part of a good body high or negative bodyload depending on your mental state. Among the more positive feelings are tingling and a sense of warmth, though in the cozy blanket way, not the overheating way.

Other

The drug’s energy level is more stimulating than sedating. It is not as stimulating as some of the psychedelic amphetamines and phenethylamines, but it is usually energetic enough to produce wakefulness, a relative lack of drowsiness, and sometimes enough energy to be active for things like hiking or dancing. Though it gives enough energy to do those activities, it is not typically coupled with a strong need or desire to be active, unlike with stimulants. Some users receive enough physically manifesting energy that they become restless and cannot get comfortable.

It is frequently said to have a wave-like nature where the visuals, euphoria, and other effects are at a high level of intensity for around 30 to 45 minutes, followed by a period of feeling fairly close to sobriety only to be swept back up in another wave soon after.

After Effects

Insomnia

A few hours of insomnia after the main effects wear off is common and it may be related to residual stimulation or perceptual changes that are distracting when trying to sleep. Some users find that although they may only be experiencing minor perceptual effects long after administration, such as 8 hours in, those effects take on a darker, scarier appearance upon turning off the lights and trying to sleep. You should expect to be awake for at least 8 to 10 hours after taking a common dose. It is preferable not to use it in the evening since the effects may become more confusing and generally problematic when mixed with greater exhaustion and sleep deprivation.

Brain Fog

It is common to feel tired or exhausted after using it, both mentally and physically. Beyond that, it can sometimes leave you feeling a bit ‘fried,’ with effects like brain fog, difficulty thinking straight, and being unproductive. Normally those effects are reset by sleep.

Day After

So long as you slept fine after using it, the hangover is typically minimal. The visuals are almost always gone by the time you wake up and normal cognition and wakefulness are restored enough to be productive. When there are after effects, they are usually at the level of feeling a bit happier and more ready for the day than usual, and those effects can sometimes last a few days. Though, a minority still feel exhausted or experience brain fog after sleeping and some users report a minor to moderate headache that usually subsides within a day.

Drug Comparisons

Mushrooms/Psilocin

The visuals with 4-HO-MET are often qualitatively similar to psilocin, but more intense dose-for-dose. It is also less deep with its mental effects, causing insight, introspection, and spiritual experiences to be more common with psilocin. The rate of easy/positive experiences may be higher and the rate of anxiety may be lower with 4-HO-MET, though some people still dislike it because it produces less of a ‘full’ trip.

4-AcO-DMT

Like with how it compares to psilocin, 4-HO-MET is usually more recreational, clearheaded, positive, and visual, but also more shallow. It is more stimulating, such that staying awake is easy, whereas 4-AcO-DMT can be drowsy.

4-HO-MiPT

The effects of 4-HO-MiPT are commonly described as being between those of 4-HO-MET and 4-AcO-DMT. It is also fairly recreational, though it can produce stronger mental effects than 4-HO-MET, while still offering good visual effects. 4-HO-MET remains preferable if you are looking for the most consistently positive, easygoing effects.

4-AcO-MET

Qualitatively they are very similar, perhaps because 4-AcO-MET hypothetically metabolizes to 4-HO-MET. 4-HO-MET is more potent and may have a faster comeup.

MDMA

Some comparisons to MDMA have been made because they can both be euphoric and entactogenic. The consistency of positive, euphoric, and entactogenic experiences is greater with MDMA, but when those effects exist with 4-HO-MET they may feel more natural and meaningful. They also have similar comeup effects with their mental and physical activation, moderate potential for anxiousness, and mood enhancement.

2C-B

They are similarly easygoing overall, but 4-HO-MET may still have a slight advantage if you are looking for recreational effects and it may have an easier bodyload.

LSD

Both are somewhat stimulating psychedelics, but the headspace of common to strong doses of LSD is stronger on average.

Combinations

Cannabis

Cannabis can strongly potentiate its effects on perception and the mind, significantly increasing the unpredictability of the effects. Even if you are a regular cannabis user, the combination should be avoided or, at the least, only a small amount of cannabis should be taken.

Other psychedelics 

A similar warning applies to combining it with other psychedelics as applies to combining it with cannabis. Although a number of success stories exist for combining it with drugs like AL-LAD, 4-AcO-DMT, or LSD, it significantly increases the unpredictability of the experience. It is best to avoid it and if that is not an option, low doses of each drug should be taken.

MDMA

Psychedelics very often provide positive experiences when combined with entactogens like MDMA and a handful of reports indicate that holds true for 4-HO-MET. There are safety concerns pertaining to a greater risk of neurotoxicity and an increased risk of seizure and cardiovascular issues, but overall the combination is acutely not very concerning so long as low to common doses are taken.

Together, 4-HO-MET can add visual and other perceptual effects normally lacking from MDMA, while MDMA can offer greater mood improvement and relaxing effects that can serve as a preferable alternative to taking sedatives to smooth out a psychedelic. The entactogenic effects of MDMA may feel more profound and meaningful when experienced from the combination.

Benzodiazepines

At low doses benzodiazepines can reduce anxious and stressful effects, but it does not take much for the visual and other beneficial effects to be dampened, so although they can be helpful as a treatment for overly anxious experiences, they are often not a great combination. And if you are trying to combine them as a way to still use psychedelics despite typically having bad experiences with them, it is better to avoid psychedelics or to find behavioral and cognitive ways to overcome whatever negative effects you get from psychedelics.

TiHKAL Entry

Alexander Shulgin described it as offering qualitative effects that are “very much like psilocin” to the extent that it would probably not be distinguishable from psilocin in a blinded study. Its wave-like nature was also noted. The entry listed its dose as 10-20 mg (oral) and its duration as 4 to 6 hours.

Papers

A 2017 paper looked at online reports of people self-treating migraines and cluster headaches with psychedelics (Andersson, 2017). It found synthetic tryptamines, including 4-HO-MET, have sometimes been used with success for this purpose, though LSD and psilocybin are far more widely used.

The drug’s recreational effects were analyzed by Kjellgren and Soussan (2011), who also utilized online reports. When the authors searched for information in 2010 they discovered no major scientific article database or Erowid’s library discussed the drug, and there were too few English language reports to adequately review the drug’s effects, so the authors used reports from Flashback.org, a popular website in Sweden. Their analysis of 25 reports produced an effect overview that was not dissimilar to the TDC overview. They also reported the most common ROA was oral and a typical dose was 25 mg.

(Andersson, 2017) – Study of the self-treatment of migraines and cluster headaches with psychedelics

  • Methods
    • Internet search that eventually led to collecting reports from Shroomery.org, Bluelight.org, and Clusterbusters.org.
    • The selection was restricted to topics initiated during the year before the study. Also, topics focused on established treatments were excluded and topics discussing potential triggers were included because some of the substances utilized in self-treatment may also act as triggers.
  • Results
    • Some synthetic tryptamines were occasionally used instead of psilocybin mushrooms because the effects were found to be more manageable. For example, one post stated “4-HO-MiPT and 4-HO-MET are said to be not as chaotic as shrooms.”
    • While less common than the use of LSD or psilocybin, some posters discussed using 4-HO-MET for migraine and cluster headache relief, similar to 4-AcO-DMT, 4-HO-MiPT, and 5-MeO-MiPT.

(Kjellgren, 2011) – A review of 4-HO-MET’s subjective effects based on online posts

  • A search was conducted in December 2010. No major scientific article database had information on the drug nor did Erowid’s library.
    • The first set of posts written in English only amounted to five pages of text, which was deemed inadequate for the review, so the authors switched to analyzing Swedish posts because posts in that language were more common.
  • 25 anonymous reports published on Flashback.org, a website in Sweden with 450,000+ members, were used. Those reports gave 82 pages of text.
  • Results
    • The dose ranged from 20 to 180 mg, with a common dose being 25 mg. The most common ROA was oral (n=21) and insufflation was second (n=3).
    • Initial effects
      • The effects gradually became more intense and the first effect involved a tingling sensation in the body, followed by an impaired ability to move. Some other bodily effects were reported: chills, lassitude, heat, and increased HR. The subjects felt different in an undefined manner and they also reported restlessness, mental activation, and nervousness.
    • Change of Perception
      • Visual distortions occurred with changes in sharpness, contrast, and color tones. Auditory changes included high and transient “ringing in the ears,” effects that were comparable to tinnitus. Flavors and sounds were deeper than usual.
      • Objects moved in wavelike patterns and vibrated. Some visual patterns occurred, first as CEVs, then as OEVs. Those patterns became more complex, turning into fractal-like forms. There was then a more intense period of perceptual alteration involving the appearance of concrete images and objects, both as CEVs and OEVs, and existing objects were perceived as different items or they melted/mixed together.
      • Sounds were distorted or experienced as if they were melting together or coming and going out of nothing. Flavors could elicit strong emotional reactions and generate new, unexpected associations. There was an impaired sense of distance and depth.
    • Unfiltered Awareness and Intensified Flow of Information
      • Perception, thoughts, and feelings increased in strength and frequency to provide a stream of info that was beyond conscious control and could not be ignored by participants, causing a sense of being overloaded. This contributed to distraction and impaired concentration and memory.
      • Normal tasks were more difficult. Text and numbers were harder to understand. Users had a more difficult time expressing their thoughts, feelings, and desires.
      • Some users could direct the unfiltered attention and focus, leading to an extreme experience of mindfulness that was very positive and could overshadow the tougher periods.
    • Lateral Cognition
      • Increased ability to see new perspectives and to question existing ideas. Cognition switched from being under the control of logical and linear processes to being more creative.
      • Participants reported insights into their patterns and habits. They also had an enhanced ability to explore new perspectives and meanings for a variety of things and they tended to question the nature of reality and their place in the universe.
    • Blurred Subject-Object Border
      • Subjective states were more easily swayed by things like music, other people, etc. Users had a greater ability to identify with and tune into other people’s emotional states.
      • A feeling of leaving one’s body was sometimes reported. Boundaries sometimes fully dissolved such that people were entirely identified with and engulfed by new internal worlds.
      • Often the most intense experiences were ultimately described in religious, spiritual, or transpersonal ways.
    • Heaven
      • Some experiences of significant euphoria, elation, and increased energy, leading to enjoyment and pleasure. Laughter and humor were common. Laughter was sometimes impossible to stop.
      • Intense feelings of deep affection and appreciation. A sense of all-encompassing love.
    • Hell
      • The intensity of the experience could generate discomfort, chaos, and a loss of control. People worried about finding their way back to sobriety and they exerted effort trying to control or restrict the experience. They could not distance themselves from anxiety, fear, and paranoia. Somatic sensations of heat, sweating, cold, tension, and increased HR were reported.
      • The participants tried different things to reduce the distress.
        • Attempts to fight it with logical reasoning generated an opposite effect.
        • Some users sought support from friends, while others used methods like breathing.
        • The most effective approach was accepting the experience and resting in what was taking place.
    • Subsiding Effects
      • A sense of relief upon returning to normal reality at the end, though sometimes people were sad and felt empty because it was over.
      • Some reports of transient discomfort: headaches, mental and physical fatigue, and insomnia.
      • Users were generally satisfied with the experience and some reported life-changing effects.


Chemistry

4-HO-MET is a simple derivative of the base tryptamine, N-methyl-N-ethyltryptamine, differing by its 4-hydroxy substitution. Tryptamine itself lacks psychedelic effects, but the addition of an N-methyl and an N-ethyl group makes it a psychedelic. From there, the potency of MET is increased by the 4-hydroxy substitution present in 4-HO-MET.

It is structurally analogous to 4-HO-DMT, otherwise known as psilocin, the primary active drug obtained from using psilocybin mushrooms. It differs from psilocin by the extension of one of its N-methyl groups by a single carbon, yielding an ethyl substitution.

It is also structurally similar to 4-AcO-MET, which has an acetoxy group in place of the hydroxy group in 4-HO-MET, yielding an acetyl ester analog of the drug. Much as the acetyl ester of psilocin, 4-AcO-DMT, is believed to metabolize to psilocin in the body, there is reason to believe 4-AcO-MET metabolizes to 4-HO-MET. That metabolic pathway is supported by at least one case where toxicology testing found 4-HO-MET was the primary drug in the user’s body following the suspected use of 4-AcO-MET (McIntyre, 2015).

4-HO-MET is typically sold as the fumarate or HCl salt.


Pharmacology

The main effects are likely mediated by the 5-HT2A receptor, where it has a high affinity and functions as a partial agonist (Rickli, 2016). It also binds with a nanomolar or low micromolar affinity to 5-HT1A, 5-HT2C, histamine H1, trace amine-associated receptor 1 (TAAR1), dopamine D2 and D3, and α1A and 2A adrenergic receptors.

It has a high affinity for the serotonin transporter, where it also has somewhat appreciable reuptake inhibition effects, although direct serotonin receptor agonism is likely a bigger contributor to its effects. It does not have monoamine releasing properties.

Affinity and efficacy values 

The following data is from Rickli (2016) and is given in nanomolar (smaller values mean higher affinity). Aside from the TAAR1 receptor, human genes were used to express the targets using HEK293 cells to obtain affinity data. For 5-HT2A activity research, human 5-HT2A was expressed in mouse embryonic fibroblasts (NIT-3T3 cells).

  • Affinity (Ki)
    • 5-HT1A: 228
    • 5-HT2A: 57
    • 5-HT2C: 141
    • SERT: 200
    • NET: 13,000
    • DAT: >26,000
    • Adrenergic α1A: 9,700
    • Adrenergic α2A: 2,400
    • D1: >25,000
    • D2: 4,000
    • D3: 6,700
    • H1: 820
    • TAAR1rat: 3,100
    • TAAR1mouse: 12,000
  • 5-HT2A receptor activation
    • EC50: 37
    • Maximum activation: 72%
  • Monoamine uptake inhibition (IC50)
    • SERT: 9,000
    • NET: 11,000
    • DAT: >100,000

Pharmacokinetics

Bruni (2018) evaluated its metabolism in vitro using pooled human liver microsomes (pHLM) and in vivo using three human forensic cases where the patient’s urine tested positive for 4-HO-MET. In vivo four metabolites were identified, with transformations include hydroxylation, glucuronidation of the parent compound, and glucuronidation of an N-oxide metabolite.

In vitro, 12 metabolites were identified, with transformations include monohydroxylation, dihydroxylation, N-oxide formation, demethylation, carboxylic acid formation, and desethylation. Three of the monohydroxylated metabolites were modified at the benzene ring of its indole structure.

(Bruni, 2018) – In vitro and in vivo metabolic pathway

  • This study used pooled human liver microsomes (pHLM) to obtain in vitro metabolism data. It looked at phase I metabolites via HPLC-IDA-HR-MS/MS)
  • In vivo metabolism was investigated using three urine samples from forensic cases testing positive for 4-HO-MET.
  • Results
    • In vivo
      • Four metabolites were identified.
      • Transformations: glucuronidation of the parent compound, glucuronidation of one of the N-oxide metabolites, and hydroxylation.
    • In vitro
      • 12 metabolites were identified. The tests used different concentrations of 4-HO-MET, and at 5 and 20 μM not all metabolites were found at significant intensities.
      • Transformations included mono-hydroxylation, dihydroxylation, N-oxide formation, demethylation, carboxylic acid formation, and desethylation.
        • Three of the monohydroxylated metabolites were modified at the 6-membered ring of the indole structure.


History

1990s

Alexander Shulgin synthesized 4-HO-MET and briefly described its subjective activity in TiHKAL, which was published in 1997.

2000s – 2010s

Internet-based vendors began selling the substance around the 2000s, leading to a fair number of online reports describing the drug at this time.

Of 436 tryptamine drug samples sent to the Spanish drug checking service Energy Control between 2006 and 2015, 19 were thought to be 4-HO-MET by the users sending them in (either from within Spain or internationally) and 17/19 were confirmed to be 4-HO-MET, while one was 4-HO-DET, and one contained no active substance (Palma-Conesa, 2017). The drug also showed up in one of two samples thought to be 4-AcO-MET.

Data from the European Union’s EMCDDA shows it began to be seized by law enforcement around the EU starting in the late 2000s. For the most part the seizures were of personal quantities. As of 2014, the drug was uncontrolled in Belgium and Bulgaria, while it was controlled in Finland, Hungary, Lithuania, Portugal, Slovakia, and Sweden (Blanckaert, 2014).

  • Reports from law enforcement to the EMCDDA, as reported by Blanckaert (2014)
    • Belgium
      • July 2014 – Analysis of a seized tablet named “Psylocibium” that contained 4-HO-MET.
    • Norway
      • December 2011 – Seizure of 0.36 g of light grey powder
    • Bulgaria
      • July 2011 – Two seizures of 0.671 g cream powder in 37 packages of a product called “Matrix”
    • Finland
      • First half of 2009 – Three seizures of powder, amounting to 0.85 g.
      • February 2009 – One seizure of 0.1 g white powder by Finnish Customs.
      • 2008 – Two seizures, totaling 0.1 g powder.
    • Sweden
      • First half of 2009 – Six seizures of powder (0.66 g)
      • 2008 – One seizure of 4.85 g powder and seven other seizures of powder amounting to 2.37 g.
      • August 2007 – One seizure of 282 g black powder.
      • March 2008 – One seizure of two capsules.

Helander (2013) reported data from Sweden’s STRIDA project during its first year of operation. That project analyzes blood and urine samples from hospital cases suspected to involve novel psychoactive substance use. Over a 12-month period beginning in 2010, there were 103 emergency department cases reported to STRIDA and the only tryptamine detected was 4-HO-MET, which was seen in eight cases. The median age of users was 22 and most people took the drug orally (n=5) or intranasally (n=3). The main symptoms associated with its use were mydriasis, agitation/restlessness, tachycardia, nausea/vomiting, and hallucinations. Half of those cases originated from the same small town in southeastern Sweden.

After a year and a half of operation, STRIDA had analyzed body fluids from 189 patients, 14 of which involved 4-HO-MET (Helander, 2014). In 11 of the 14, the drug was used by itself and those cases led to minor (n=7) or moderate (n=4) symptoms, which usually resolved with supportive care, though sometimes sedatives (e.g. diazepam and/or propofol) were provided.

Surveys given to Spanish research chemical users between August 2010 and June 2011 revealed 4-HO-MET was a fairly uncommon drug (Gonzalez, 2013). Among 230 people, 2C-B and methylone were used by 80% and 40%, respectively, whereas 3% of respondents reported taking 4-HO-MET.

STRIDA’s analysis of body fluids and drug products from 173 cases between 2010 and 2015 found 4-HO-MET was detected in powder on four occasions, occurring in 2010, 2011, and 2012 (Backberg, 2018).

Sweden has historically been a major market for the drug, but interest in it significantly declined after it became a controlled substance in May 2012, based on an analysis of forum posts (Ledberg, 2015).

As of 2019, it is often still an uncontrolled substance and it remains one of the more popular RC psychedelics globally.

(Backberg, 2018) – Analysis of drug products and body fluids by Sweden’s STRIDA project.

  • Background
    • Clinicians who contact the Poisons Information Centre in Sweden regarding acute intoxication with suspected novel psychoactive drugs are asked to provide blood and urine for free analysis to screen for psychoactive drugs.
  • 251 products and body fluids were analyzed from 173 acute intoxication cases that occurred in 2010 to 2015.
  • Results
    • Of the 251, 151 (60%) were confirmed to be novel psychoactive substances. In 70% only one substance was present, while in 30% there were 2 or more substances present.
    • 4-HO-MET was detected in powder form in 4 instances (occurring in 2010, 2011, and 2012).

 

(Palma-Conesa, 2017) – Review of the contents of drug samples submitted to Energy Control between 2006 and 2015.

  • Background
    • Energy Control offers free, anonymous drug checking to people in Spain and it offers a paid drug checking service to people internationally.
  • 25,296 samples were delivered between 2006 and 2015. Of those, 436 were tryptamines.
  • Results
    • 4-AcO-DMT was the most commonly expected unregulated tryptamine (i.e. not psilocin, DMT, psilocybin, DET, or α-ET).
    • 19 (8%) were delivered as 4-HO-MET.
      • Of these, 17 were confirmed to be 4-HO-MET, while 1 was 4-HO-DET, and 1 contained no active substance.
    • Also, 4-HO-MET showed up in 1 of 2 samples delivered as 4-AcO-MET.

 

(Ledberg, 2015) – Interest in 4-HO-MET appeared to decline in Sweden after it became a controlled drug.

  • Methods
    • Reviewing posts on Flashback.org, a large internet forum in Sweden, featuring over 850,000 members. The study aimed to see how a change in legality affected consumer interest during the preceding five years.
    • 60+ substances had changed from legal to illicit during this time, but the study only looked at those which had been regularly discussed on the forum. The list was narrowed down to MDPV, methylone, 4-MEC, 4-HO-MET, MXE, 6-APB, AH-7921, and 3-MMC.
  • Results
    • 4-HO-MET
      • It appears to have been introduced early in 2008 and from that point forward interest in the drug fluctuated. There were long periods of high activity, i.e. 10+ posts per day about the drug. After it was controlled as a narcotic substance on May 1, 2012, activity about the substance on the forum decreased to very low levels.
    • General
      • There was a pattern for substances to be discussed far less once they were scheduled. For 7/8 substances a strong statistical association between legality change and activity on the forum was seen.

 

(Helander, 2014) – Analysis of body fluids by Sweden’s STRIDA project

  • Results
    • From January 2010 to August 2011 (the first 1.5 years of STRIDA) there were 1147 inquiries covering >900 unique cases and in 466 patients NPS exposure was suspected.
      • Body fluids from 189 patients were received. In 97%, information was given about clinical symptoms and treatment.
    • Psilocin was detected in 3 cases. Surpassing that, 4-HO-MET was detected in 14 cases.
      • In 11/14 the drug was present in a single-substance intoxication and those cases were graded as minor (n=7) or moderate (n=4) poisonings. The symptoms typically resolved with supportive care, though sometimes diazepam was used for sedation and propofol was occasionally added as well.

 

(Gonzalez, 2013) – Survey regarding novel psychoactive substance use among Spanish research chemical users

  • A 16-question survey was created based on information obtained from 12 users who had extensive experience with RCs. The survey was given to adults legally residing in Spain who spoke Spanish as their first language and who had used an RC at least once.
  • Results
    • Between August 2010 and June 2011, 230 surveys were completed. The respondents were reached via trance music festivals (44% from Boom Festival or Sol Festival), via Energy Control’s site in Barcelona (15%), or via an online drug forum called Cannabiscafe (42%).
    • 2.6% of respondents reported taking 4-HO-MET. For comparison: 2C-B (80%), methylone (40%), 2C-I (40%), mephedrone (35%), 2C-E (26%), AMT (16%).
    • And for drug combinations, 0.4% reported using 4-HO-MET with mephedrone. For comparison: 2C-B + MDMA (28%), 2C-B + amphetamine (7%), 2C-B + LSD (6%).

 

(Helander, 2013) – Analysis of data from Sweden’s STRIDA project during its first year of operation.

  • Background
    • In January 2010, a joint nationwide project called STRIDA was created to address the issue of novel psychoactive drugs, partly by using multi-component LC-MS/MS to identify substances encountered in clinical settings. The project was started by the Karolinska Institutet, the Karolinska University Laboratory, and the Swedish Poisons Information Centre.
  • Results
    • During its first 12 months of operation the project was notified of 103 cases where patients presented to emergency departments across the country.
      • 36% of cases involved synthetic cannabinoids, 14% involved substituted cathinones, and 4% involved kratom. In 32% the drug was listed as “unknown.”
    •  Substituted tryptamines
      • The only tryptamine encountered at this time was 4-HO-MET. There were eight cases, with the age range being 17-32 years old (median=22). Oral (n=5) and insufflation (n=3) were the ROA.
      • The main symptoms were mydriasis, agitation/restlessness, tachycardia, nausea/vomiting, and hallucinations.
      • Half of the cases originated from the same small town in southeastern Sweden.


Legality (as of August 2019)

Australia: Not specifically controlled but it may fall under analog laws.

Canada: Uncontrolled

United Kingdom: Class A due to a general law controlling tryptamines.

United States: Unscheduled, but it will likely fall under the Federal Analogue Act when intended for human consumption.


Safety

Because very little is known about its safety, it should be taken at common doses, infrequently, and without combinations.

Considering its known effects and pharmacology, its risks should be largely similar to psilocin and LSD. This means regular doses carry some potential of panic, psychosis, tachycardia, hypertension, and hyperthermia.

And overdoses can be expected to frequently trigger psychotic symptoms and more rarely they could conceivably be associated with cardiovascular complications,  seizures, dangerous hyperthermia, excessive muscle tension, and kidney damage, though most of those risks are only hypothetical based on its pharmacology.

Adverse Effect Reports

One formal case report of psychosis was published by Taljemark (2012). It described as teenager who used ~100 mg, leading to dangerously psychotic symptoms and psychological problems that gradually improved over the course of a week in the hospital. There was no lasting negative effect, but his acute state was severe enough that different circumstances could have led to dangerous or lethal outcomes.

(Taljemark, 2012) – A case of psychosis triggered by a 4-HO-MET overdose

  • A 17-year-old was found in his underwear along a motorway by police. He said he would not talk to anyone and he proceeded to be mute and apathetic. He was admitted to the acute medical department.
    • Prior to this he was psychiatrically and physically well.
  • Admission: Blood tests and CT head scan were normal. Urine toxicology screen was positive for THC and cocaine (cocaine had been taken two days prior). He was given supportive care.
  • Evening of the admission day: After being apathetic throughout the day he jumped 3-4 m from a roof. After being found outside the hospital a CT scan showed a fractured right radius and small right-sided pneumothorax, but no intracranial pathology. A neurological exam and EEG were normal.
  • He was detained and brought to the psychiatric ICU because of severe agitation and presumed suicidality. He then became apathetic again. Because he needed further supportive treatment he was brought back to the acute medical care unit.
  • 2 days later: Medical condition stabilized. A psychiatric assessment showed he was mute and withdrawn. Antipsychotics were withheld due to uncertainty about the diagnosis and his already subdued state. He was admitted to the Child and Adolescent Psychiatry Emergency Unit.
  • Over the next week: Gradual improvement, with social interaction normalizing, though he claimed to have retrograde amnesia.
  • 11 days after admission (discharge day): No ongoing psychiatric illness detected. He explained the situation. He had received 4-HO-MET from a friend, who ordered it online, and ~100 mg was inhaled the evening preceding the admission. When he began seeing doors in the bookcase in front of him, he panicked and left the apartment. While walking the streets he perceived them being covered with a meter of water and filled with snakes. He was distressed, lonely, and felt persecuted. He sensed insects under his skin and his heart jumping out of his chest.
    • He remembered his admission to the hospital, which was followed by hearing his father’s voice repeating “you have never dared to dive,” which led to him climbing on the roof and ‘diving’ off of it to prove his father wrong.
    • Acute psychosis then subsided, but he continued to be paranoid about the food and drinks he was given in the ward for several days into his admission.
  • 2 months later: No evidence of residual problems, so he was discharged from outpatient services.

Fatalities

No fatalities primarily attributed to 4-HO-MET have been reported in the literature as of August 2019. One fatality attributed to polydrug use involving 4-HO-MET has been described, but 4-MeO-PCP may have played a larger role in that case. (McIntyre, 2015).

(McIntyre, 2015) – Fatality associated with polydrug intoxication. Primarily attributed to 4-MeO-PCP, but 4-HO-MET was present.

  • 54-year-old male found unresponsive in bed during a welfare check. His medical history included hypertension and substance use–he was known to take alcohol, cannabis, methamphetamine, and PCP. His mother reported he ordered 3-MeO-PCP online and during an earlier ED visit for abnormal behavior he confessed to using 3-MeO-PCP to self-treat depression.
  • Autopsy showed pulmonary congestion and edema, along with foam in his mouth and airway, which were deemed consistent with acute drug intoxication.
  • Toxicology
    • 4-MeO-PCP was initially detected via ELISA screening for PCP. Its presence was confirmed using MS.
    • 4-HO-MET was presumptively identified from peripheral blood using data from the SWGDRUG mass spectral library and its presence was then confirmed.
    • White powder residue had been collected from the decedent’s home and it was identified by the DEA as 4-AcO-MET, with neither 3-MeO-PCP nor 4-MeO-PCP detected.
      • It is suspected 4-AcO-MET rapidly hydrolyzes to free phenolic 4-HO-MET via the action of serum esterases, which could explain why 4-HO-MET was detected in body fluids, not 4-AcO-MET.
    • Therapeutic concentrations of venlafaxine, olanzapine, lorazepam, and hydroxyzine were present in peripheral blood.
  • Cause of death: Accidental acute mixed drug intoxication.

Risky Combinations (list is not exhaustive)

  • Other psychedelics
  • Stimulants
  • MAOIs
  • Tramadol

References

Andersson, M., Persson, M., & Kjellgren, A. (2017). Psychoactive substances as a last resort—a qualitative study of self-treatment of migraine and cluster headaches. Harm Reduction Journal, 14(1), 60. https://doi.org/10.1186/s12954-017-0186-6

Bäckberg, M., Jönsson, K.-H., Beck, O., & Helander, A. (2018). Investigation of drug products received for analysis in the Swedish STRIDA project on new psychoactive substances. Drug Testing and Analysis, 10(2), 340–349. https://doi.org/10.1002/dta.2226

Blanckaert, P. (2014). 4-HO-MET, (July). https://www.me-assist.com/wp-content/uploads/2014/07/Fact-Sheet-4-HO-MET.pdf

Bruni, P. S., Grafinger, K. E., Nussbaumer, S., König, S., Schürch, S., & Weinmann, W. (2018). Study of the in vitro and in vivo metabolism of 4-HO-MET. Forensic Science International, 290, 103–110. https://doi.org/10.1016/j.forsciint.2018.06.037

González, D., Ventura, M., Caudevilla, F., Torrens, M., & Farre, M. (2013). Consumption of new psychoactive substances in a Spanish sample of research chemical users. Human Psychopharmacology: Clinical and Experimental, 28(4), 332–340. https://doi.org/10.1002/hup.2323

Helander, A., Bäckberg, M., Hultén, P., Al-Saffar, Y., & Beck, O. (2014). Detection of new psychoactive substance use among emergency room patients: Results from the Swedish STRIDA project. Forensic Science International, 243, 23–29. https://doi.org/10.1016/j.forsciint.2014.02.022

Helander, A., Beck, O., Hägerkvist, R., & Hultén, P. (2013). Identification of novel psychoactive drug use in Sweden based on laboratory analysis – initial experiences from the STRIDA project. Scandinavian Journal of Clinical and Laboratory Investigation, 73(5), 400–406. https://doi.org/10.3109/00365513.2013.793817

Kjellgren, A., & Soussan, C. (2011). Heaven and Hell—A Phenomenological Study of Recreational Use of 4-HO-MET in Sweden. Journal of Psychoactive Drugs, 43(3), 211–219. https://doi.org/10.1080/02791072.2011.605699

Ledberg, A. (2015). The interest in eight new psychoactive substances before and after scheduling. Drug and Alcohol Dependence, 152, 73–78. https://doi.org/10.1016/j.drugalcdep.2015.04.020

McIntyre, I. M., Trochta, A., Gary, R. D., Storey, A., Corneal, J., & Schaber, B. (2015). A Fatality Related to Two Novel Hallucinogenic Compounds: 4-Methoxyphencyclidine and 4-Hydroxy- N -methyl- N -ethyltryptamine. Journal of Analytical Toxicology, 39(9), 751–755. https://doi.org/10.1093/jat/bkv089

Palma-Conesa, Á. J., Ventura, M., Galindo, L., Fonseca, F., Grifell, M., Quintana, P., … Torrens, M. (2017). Something New about Something Old: A 10-Year Follow-Up on Classical and New Psychoactive Tryptamines and Results of Analysis. Journal of Psychoactive Drugs, 49(4), 297–305. https://doi.org/10.1080/02791072.2017.1320732

Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E. (2016). Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology, 26(8), 1327–1337. https://doi.org/10.1016/j.euroneuro.2016.05.001

Täljemark, J., & Johansson, B. A. (2012). Drug-induced acute psychosis in an adolescent first-time user of 4-HO-MET. European Child & Adolescent Psychiatry, 21(9), 527–528. https://doi.org/10.1007/s00787-012-0282-9

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