Efavirenz

Antiretroviral medication

Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is sold both by itself and in combination as efavirenz/emtricitabine/tenofovir. It is taken by mouth.

Common side effects include rash, nausea, headache, feeling tired, and trouble sleeping. Some of the rashes may be serious such as Stevens–Johnson syndrome. Other serious side effects include depression, thoughts of suicide, liver problems, and seizures. It is not safe for use during pregnancy. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and works by blocking the function of reverse transcriptase.

Efavirenz was approved for medical use in the United States in 1998, and in the European Union in 1999. It is on the World Health Organization's List of Essential Medicines. As of 2016, it is available as a generic medication.

How It Feels

Efavirenz does not announce itself as a psychoactive experience in any conventional sense. It arrives instead as a quiet disturbance in the architecture of sleep and waking. In the first days and weeks of treatment, the most common experience is a strange vivification of the hypnagogic state, that liminal territory between wakefulness and sleep. As you lie in bed, the darkness behind closed eyelids begins to populate itself with unusually vivid imagery. Colors bloom and shift. Faces may appear with uncanny detail and then dissolve. The transition into sleep becomes a corridor of hallucinatory fragments that feel more substantial and persistent than ordinary pre-sleep imagery.

Dreams themselves become extraordinary in their vividness, complexity, and emotional intensity. They are often described as cinematic, as though the sleeping mind has gained access to a more powerful rendering engine. Nightmares are common, and they carry a visceral, embodied quality that can linger well into the morning. Some users report lucid dreaming, where awareness of the dream state coexists with the dreaming itself. Upon waking, there may be a period of confusion in which the dream reality and waking reality seem equally plausible, and the boundary between the two takes several minutes to reassert itself.

During waking hours, the effects are subtler but still perceptible. There is a mild dizziness or lightheadedness that ebbs and flows without clear pattern. Concentration may feel slightly impaired, as though a thin gauze has been drawn between the mind and its objects of focus. Some users describe a gentle derealization, a sense that the world looks faintly artificial or staged, like a set in a play about ordinary life. Colors may appear marginally more vivid, and there is occasionally a barely perceptible wavering at the edges of the visual field. These effects are mild enough that many users learn to ignore them, but they contribute to an overall sense that baseline consciousness has been subtly but persistently altered.

These neuropsychiatric effects typically diminish over the first two to four weeks of treatment as the body adjusts, though some users report that the vivid dreams persist indefinitely. The experience is not sought out recreationally and is generally regarded as a tolerable side effect rather than a desired state. Nonetheless, for those who pass through it, efavirenz offers a curious window into how pharmacological tinkering with neural circuitry can produce perceptual changes that, while modest in scale, are genuinely strange.

Pharmacology

Pharmacodynamics

Anti-HIV effects Efavirenz falls in the NNRTI class of antiretrovirals. Both nucleoside and non-nucleoside RTIs inhibit the same target, the reverse transcriptase enzyme, an essential viral enzyme which transcribes viral RNA into DNA. Unlike nucleoside RTIs, which bind at the enzyme's active site, NNRTIs act allosterically by binding to a distinct site away from the active site known as the NNRTI pocket.

Efavirenz is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class.

As most NNRTIs bind within the same pocket, viral strains which are resistant to efavirenz are usually also resistant to the other NNRTIs, nevirapine and delavirdine. The most common mutation observed after efavirenz treatment is K103N, which is also observed with other NNRTIs. Nucleoside reverse-transcriptase inhibitors (NRTIs) and efavirenz have different binding targets, so cross-resistance is unlikely; the same is true with regard to efavirenz and protease inhibitors.

Neuropsychiatric effects Efavirenz has been found to have affinity for a variety of targets to varying degrees and appears to act as an antagonist of the serotonin 5-HT2A (specifically Gq signaling), 5-HT2B, 5-HT2C, and 5-HT3 receptors, as an inverse agonist of the serotonin 5-HT6 receptor, as a dual GABAA receptor positive allosteric modulator and orthosteric site antagonist, as a serotonin–dopamine reuptake inhibitor (SDRI), as a vesicular monoamine transporter 2 (VMAT2) inhibitor, as a monoamine oxidase inhibitor (MAOI) of MAO-A, and as an antagonist of the muscarinic acetylcholine M1 and M3 receptors. Efavirenz produces the head-twitch response, a behavioral proxy of serotonergic psychedelic effects, in animals, and can partially substitute for LSD and MDMA in animal drug discrimination tests. Induction of the head-twitch response and substitution for LSD by efavirenz can be abolished by serotonin 5-HT2A receptor antagonists or serotonin 5-HT2A receptor knockout. Efavirenz does not substitute for cocaine or carisoprodol. The drug is not self-administered and does not produce conditioned place preference (CPP) in animals.

As of 2016 the mechanism of efavirenz's neuropsychiatric adverse effects was not clear. It appears to produce neurotoxicity, possibly by interfering with mitochondrial function, which may in turn possibly be caused by inhibiting creatine kinase but also possibly by disrupting mitochondrial membranes or by interfering with nitric oxide signalling. Some neuropsychiatric adverse effects may be mediated through cannabinoid receptors, or through activity at the serotonin 5-HT2A receptor, but efavirenz interacts with many central nervous system targets, so this is not clear. The neuropsychiatric adverse effects are dose-dependent. Although efavirenz appears to act as a serotonin 5-HT2A receptor antagonist, it has been suggested that it might exert functional selectivity and act as an agonist of the receptor for certain signaling pathways, which could in turn explain its hallucinogenic and LSD-like effects. However, this hypothesis remains to be evaluated. Conversely, research suggests that efavirenz may actually be a partial agonist of the serotonin 5-HT2A receptor. The effects of efavirenz in animals and humans are consistent with it being a serotonergic psychedelic.

Pharmacokinetics The onset of action of efavirenz is 3 to 5hours and its elimination half-life is 52 to 76hours with a single dose and 40 to 55hours with continuous administration. The shorter half-life with chronic administration may be due to induction of cytochrome P450 enzymes by efavirenz.

Detection Methods

Urine Detection

Efavirenz is an antiretroviral medication (non-nucleoside reverse transcriptase inhibitor) used in HIV treatment that has documented psychoactive properties. As a prescribed pharmaceutical, it is routinely detectable by standard clinical pharmacology methods. Urinary metabolites of efavirenz, primarily 8-hydroxyefavirenz, can be detected for several days after dosing. In the context of chronic therapeutic use, metabolites are continuously present. Efavirenz is NOT detected by standard recreational drug immunoassay screens but has been reported to cause false positive results on some cannabinoid immunoassays.

Blood and Serum Detection

Efavirenz has a long plasma half-life of 40 to 55 hours after multiple doses, making it detectable in blood for several days after discontinuation. Therapeutic drug monitoring by LC-MS/MS or HPLC is well-established. Plasma concentrations above 4 mg/L are associated with increased CNS side effects including the psychoactive and dissociative properties.

Standard Drug Panel Inclusion

Efavirenz is NOT included as a target on standard drug panels. However, it is notable for its potential to cause false positive results on some THC (cannabinoid) immunoassays. This cross-reactivity has been documented in multiple published studies and should be considered when interpreting positive cannabinoid screens in individuals taking efavirenz.

Confirmatory Methods

GC-MS and LC-MS/MS confirmatory testing will not confirm THC in cases of efavirenz cross-reactivity, correctly resolving the false positive. Therapeutic drug monitoring methods for efavirenz are well-established and widely available through clinical reference laboratories. No specialized forensic methods are required.

Reagent Testing (Harm Reduction)

Reagent testing is generally not applicable to efavirenz as it is a pharmaceutical product typically obtained in manufactured tablet form. The Marquis, Mecke, and Mandelin reagents may produce various color reactions with efavirenz but these are not well-characterized in harm reduction literature. Identification of efavirenz tablets is best accomplished through pill identification databases using imprint codes, color, and shape.

Interactions

Substance	Status	Note
2-Aminoindane	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
2-FA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
2-FEA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
2-FMA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
2,5-DMA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
2C-H	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
3-FA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
3-FEA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
3-FMA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
3-FPM	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
3-MMC	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
3,4-CTMP	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
4-FA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
4-FMA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
4-MMC	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
4F-EPH	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
4F-MPH	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
5-APB	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
5F-AKB48	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
5F-PB-22	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
6-APDB	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
8-Chlorotheophylline	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
A-PHP	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
A-PVP	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
AB-FUBINACA	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
Adrafinil	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Amphetamine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Anandamide	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
APICA	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
Armodafinil	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Atropa belladonna	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Benzydamine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Bromantane	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Butylone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Caffeine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Cannabidiol	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
Cannabis	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
Cocaine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Cyclazodone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Datura	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Desoxypipradrol	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Dextroamphetamine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Dichloropane	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Diphenhydramine	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Ephedrine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Ephylone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
ETH-CAT	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Ethylone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Ethylphenidate	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Fenethylline	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Harmala alkaloid	Caution	MAOIs dramatically potentiate psychedelics; drastically reduce dose and exercise extreme caution
Hexedrone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Isopropylphenidate	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
JWH-018	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
JWH-073	Caution	Cannabis can unpredictably intensify psychedelic effects and increase anxiety
Kratom	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Lisdexamfetamine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
MAOI	Caution	MAOIs dramatically potentiate psychedelics; drastically reduce dose and exercise extreme caution
MCPP	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
MDA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
MDMA	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
MDPV	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Mephedrone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Methamphetamine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Methcathinone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Methiopropamine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Methylnaphthidate	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Methylone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Methylphenidate	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Mexedrone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Mirtazapine	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Modafinil	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Myristicin	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
N-Ethylhexedrone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
N-Methylbisfluoromodafinil	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
NEP	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Nicotine	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
NM-2-AI	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Oxiracetam	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Peganum harmala	Caution	MAOIs dramatically potentiate psychedelics; drastically reduce dose and exercise extreme caution
Pentedrone	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Phenylpiracetam	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
Rhodiola Rosea	Caution	Increases anxiety, cardiovascular stress, and psychological intensity
1,3-Butanediol	Low Risk & Synergy	Cross-tolerance exists; effects compound
1B-LSD	Low Risk & Synergy	Cross-tolerance exists; effects compound
1cP-AL-LAD	Low Risk & Synergy	Cross-tolerance exists; effects compound
1cP-LSD	Low Risk & Synergy	Cross-tolerance exists; effects compound
1cP-MiPLA	Low Risk & Synergy	Cross-tolerance exists; effects compound
1P-ETH-LAD	Low Risk & Synergy	Cross-tolerance exists; effects compound
1P-LSD	Low Risk & Synergy	Cross-tolerance exists; effects compound
1V-LSD	Low Risk & Synergy	Cross-tolerance exists; effects compound
2-Fluorodeschloroketamine	Low Risk & Synergy	Produces unique synergistic effects; often combined
25B-NBOH	Low Risk & Synergy	Cross-tolerance exists; effects compound
25B-NBOMe	Low Risk & Synergy	Cross-tolerance exists; effects compound
25C-NBOH	Low Risk & Synergy	Cross-tolerance exists; effects compound
25C-NBOMe	Low Risk & Synergy	Cross-tolerance exists; effects compound
25D-NBOMe	Low Risk & Synergy	Cross-tolerance exists; effects compound
25E-NBOH	Low Risk & Synergy	Cross-tolerance exists; effects compound
25I-NBOH	Low Risk & Synergy	Cross-tolerance exists; effects compound
25I-NBOMe	Low Risk & Synergy	Cross-tolerance exists; effects compound
25N-NBOMe	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-B	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-B-FLY	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-C	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-D	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-E	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-I	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-P	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-T	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-T-2	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-T-21	Low Risk & Synergy	Cross-tolerance exists; effects compound
2C-T-7	Low Risk & Synergy	Cross-tolerance exists; effects compound
3-Cl-PCP	Low Risk & Synergy	Produces unique synergistic effects; often combined
3-HO-PCE	Low Risk & Synergy	Produces unique synergistic effects; often combined
3-HO-PCP	Low Risk & Synergy	Produces unique synergistic effects; often combined
3-MeO-PCE	Low Risk & Synergy	Produces unique synergistic effects; often combined
3-MeO-PCMo	Low Risk & Synergy	Produces unique synergistic effects; often combined
3-MeO-PCP	Low Risk & Synergy	Produces unique synergistic effects; often combined
3C-E	Low Risk & Synergy	Cross-tolerance exists; effects compound
3C-P	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-AcO-DET	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-AcO-DiPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-AcO-DMT	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-AcO-MET	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-AcO-MiPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-HO-DET	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-HO-DiPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-HO-DPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-HO-EPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-HO-MET	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-HO-MiPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-HO-MPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
4-MeO-PCP	Low Risk & Synergy	Produces unique synergistic effects; often combined
5-MeO-DALT	Low Risk & Synergy	Cross-tolerance exists; effects compound
5-MeO-DiBF	Low Risk & Synergy	Cross-tolerance exists; effects compound
5-MeO-DiPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
5-MeO-DMT	Low Risk & Synergy	Cross-tolerance exists; effects compound
5-MeO-MiPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
6-APB	Low Risk & Synergy	Cross-tolerance exists; effects compound
AL-LAD	Low Risk & Synergy	Cross-tolerance exists; effects compound
ALD-52	Low Risk & Synergy	Cross-tolerance exists; effects compound
Allylescaline	Low Risk & Synergy	Cross-tolerance exists; effects compound
Ayahuasca	Low Risk & Synergy	Cross-tolerance exists; effects compound
Bromo-DragonFLY	Low Risk & Synergy	Cross-tolerance exists; effects compound
Bufotenin	Low Risk & Synergy	Cross-tolerance exists; effects compound
Deschloroketamine	Low Risk & Synergy	Produces unique synergistic effects; often combined
DET	Low Risk & Synergy	Cross-tolerance exists; effects compound
Dextromethorphan	Low Risk & Synergy	Produces unique synergistic effects; often combined
Diphenidine	Low Risk & Synergy	Produces unique synergistic effects; often combined
DiPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
DMT	Low Risk & Synergy	Cross-tolerance exists; effects compound
DOB	Low Risk & Synergy	Cross-tolerance exists; effects compound
DOC	Low Risk & Synergy	Cross-tolerance exists; effects compound
DOI	Low Risk & Synergy	Cross-tolerance exists; effects compound
DOM	Low Risk & Synergy	Cross-tolerance exists; effects compound
DPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
Ephenidine	Low Risk & Synergy	Produces unique synergistic effects; often combined
EPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
Escaline	Low Risk & Synergy	Cross-tolerance exists; effects compound
ETH-LAD	Low Risk & Synergy	Cross-tolerance exists; effects compound
HXE	Low Risk & Synergy	Produces unique synergistic effects; often combined
Ibogaine	Low Risk & Synergy	Cross-tolerance exists; effects compound
Inhalants	Low Risk & Synergy	Produces unique synergistic effects; often combined
Ketamine	Low Risk & Synergy	Produces unique synergistic effects; often combined
LAE-32	Low Risk & Synergy	Cross-tolerance exists; effects compound
LSA	Low Risk & Synergy	Cross-tolerance exists; effects compound
LSD	Low Risk & Synergy	Cross-tolerance exists; effects compound
LSM-775	Low Risk & Synergy	Cross-tolerance exists; effects compound
LSZ	Low Risk & Synergy	Cross-tolerance exists; effects compound
Memantine	Low Risk & Synergy	Produces unique synergistic effects; often combined
Mescaline	Low Risk & Synergy	Cross-tolerance exists; effects compound
MET	Low Risk & Synergy	Cross-tolerance exists; effects compound
Methallylescaline	Low Risk & Synergy	Cross-tolerance exists; effects compound
Methoxetamine	Low Risk & Synergy	Produces unique synergistic effects; often combined
Methoxphenidine	Low Risk & Synergy	Produces unique synergistic effects; often combined
MiPLA	Low Risk & Synergy	Cross-tolerance exists; effects compound
MiPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
MPT	Low Risk & Synergy	Cross-tolerance exists; effects compound
MXiPr	Low Risk & Synergy	Produces unique synergistic effects; often combined
Nitrous	Low Risk & Synergy	Produces unique synergistic effects; often combined
O-PCE	Low Risk & Synergy	Produces unique synergistic effects; often combined
PARGY-LAD	Low Risk & Synergy	Cross-tolerance exists; effects compound
PCE	Low Risk & Synergy	Produces unique synergistic effects; often combined
PCP	Low Risk & Synergy	Produces unique synergistic effects; often combined
PRO-LAD	Low Risk & Synergy	Cross-tolerance exists; effects compound
Psilocybin Mushrooms	Low Risk & Synergy	Cross-tolerance exists; effects compound
Codeine	Low Risk & No Synergy	No significant pharmacological interaction; opioids may slightly dull the psychedelic experience
Fentanyl	Low Risk & No Synergy	No significant pharmacological interaction; opioids may slightly dull the psychedelic experience
Heroin	Low Risk & No Synergy	No significant pharmacological interaction; opioids may slightly dull the psychedelic experience
Morphine	Low Risk & No Synergy	No significant pharmacological interaction; opioids may slightly dull the psychedelic experience
Oxycodone	Low Risk & No Synergy	No significant pharmacological interaction; opioids may slightly dull the psychedelic experience
Alcohol	Low Risk & Decrease	Depressants dull psychedelic effects; benzodiazepines are commonly used as trip-killers
Alprazolam	Low Risk & Decrease	Depressants dull psychedelic effects; benzodiazepines are commonly used as trip-killers
Clonazepam	Low Risk & Decrease	Depressants dull psychedelic effects; benzodiazepines are commonly used as trip-killers
Diazepam	Low Risk & Decrease	Depressants dull psychedelic effects; benzodiazepines are commonly used as trip-killers
GHB	Low Risk & Decrease	Depressants dull psychedelic effects; benzodiazepines are commonly used as trip-killers
Lorazepam	Low Risk & Decrease	Depressants dull psychedelic effects; benzodiazepines are commonly used as trip-killers

Showing 197 key interactions out of 240 total.

Toxicity & Safety

Further information: Research chemicals § Toxicity and harm potential, and Responsible use § Hallucinogens Efavirenz has a low toxicity relative to dose. Like many HIV medications, efavirenz may cause liver toxicity at high doses or after chronic use.

It is strongly recommended that one use harm reduction practices when using this drug.

Tolerance and addiction potential

Efavirenz is not known to be habit-forming. While developing a tolerance to efavirenz is extremely rare, abusing efavirenz may cause HIV to become resistant to the drug and increase the viral load in patients with HIV.

Dangerous interactions

As efavirenz may cause hepatoxicity at high doses or after chronic use, it is not recommended to take this substance concurrently with other substances that may cause hepatoxicity. Efavirenz is an inducer of the CYP2B6 and CYP3A4 enzymes of the cytochrome P450 system, and as a result may change the metabolism of drugs metabolized by them. Consuming garlic may decrease serum levels of efavirenz.

Serotonin syndrome risk

Efavirenz is a weak serotonin reuptake inhibitor, so it is possible that combining heavy doses of efavirenz and the substances listed below may result in serotonin syndrome. Combinations with the following substances can cause dangerously high serotonin levels. Serotonin syndrome requires immediate medical attention and can be fatal if left untreated.

MAOIs - Such as banisteriopsis caapi, syrian rue, phenelzine, selegiline, and moclobemide.
Serotonin releasers - Such as MDMA, 4-FA, methamphetamine, methylone and αMT.
SSRIs - Such as citalopram and sertraline
SNRIs - Such as tramadol and venlafaxine
5-HTP

Addiction Potential

not known to be habit-forming

Overdose Information

Fatal overdose from Efavirenz alone, at doses within the typical recreational range, is extremely unlikely based on the available evidence for classical psychedelics. The therapeutic index for most psychedelics is very wide.

However, psychological emergencies can occur and require appropriate response:

Severe anxiety, panic, or psychotic episodes
Dangerous behavior due to impaired reality testing
Self-harm in the context of a distressing experience

Emergency management: If someone is experiencing a severe adverse reaction, move them to a calm, quiet environment. Speak reassuringly. Do not restrain unless there is immediate danger. Benzodiazepines (if available and the person is conscious and able to swallow) can reduce acute anxiety. If psychotic symptoms, self-harm risk, or medical distress is present, seek emergency medical attention.Medical attention: Seek help immediately for seizures, extremely elevated body temperature, signs of serotonin syndrome (agitation, tremor, diarrhea, rapid heart rate), or if the substance consumed is uncertain.

Full	Unknown
Half	Unknown
Zero	Unknown

Quick Dosage

Dosage

smoked

Duration

smoked

How It Feels

Subjective Effects

Physical Effects

Physical(6)

Cognitive & Perceptual Effects

Visual(14)

Pharmacology

Detection Methods

Urine Detection

Blood and Serum Detection

Standard Drug Panel Inclusion

Confirmatory Methods

Reagent Testing (Harm Reduction)

Interactions

History

Harm Reduction

Toxicity & Safety

Addiction Potential

Overdose Information

Tolerance

Legal Status

Experience Reports (2)

Tips (3)

See Also

References (6)

Frequently Asked Questions

Cognitive(8)

Auditory(3)

Transpersonal(1)