Psilocybin
Description
Psilocybin is a naturally occurring psychedelic compound found in certain mushrooms
Chemical Class
Tryptamine
Mechanism of Action
Active at serotonin receptors: 5HT1a, 2a and 2c mainly, with 5HT2a activity being mainly responsible for subjective effects
Source
Found in and first isolated from Central American mushrooms
Clinical Trial Doses
Typically:
1mg for placebo/ sub perceptual
10mg low dose
25mg provisional therapeutic dose
Route of Administration
Oral
Onset of Action
20 – 60 mins depending on dose, how recently someone has eaten and more and there are exceptions to this time frame
Duration of Subjective Experience
4-6 hours typically
Metabolism
Liver
Therapeutic Uses/ Current Clinical Trial Indications
Phase III: Treatment Resistant Depression
Phase II: Major Depressive Disorder, Generalised Anxiety Disorder, Alcohol Use Disorder, PTSD, Adjustment disorder due to cancer disgnosis, Anorexia Nervosa, Binge Eating disorder, Opioid Use Disorder, Demoralisation Syndrome, Fragile X Syndrome (microdose)
Phase I: Cluster Headache, Headache Disorder, OCD
Side Effects
Nausea, headache, anxiety, distress, some increase in heart rate and blood pressure
Contraindications (mainly)
History of psychosis
Cardiovascular issues
Safety Profile
Low toxicity
Well-tolerated
Dependence Potential
Low
Tolerance
Rapid development
Drug Interactions
Potentially SSRIs and other serotonergic drugs
Lysergic acid diethylamide (LSD)
Chemical Class
Tryptamine
Mechanism of Action
Active mainly at serotonin and dopamine receptors: 5-HT1a, 2a, 2b, 2c, 5a and 6. 5HT2a and possible D2 activity is thought to be responsible for subjective effects
Source
Synthetic
Clinical Trial Doses
Typically:
Low Dose: 25-50 micrograms
Provisional therapeutic dose 100 micrograms
High dose 200 micrograms
Route of Administration
Oral
Sublingual
Onset of Action
20-60 minutes
Duration of Subjective Experience
8-12 hours
Metabolism
Liver
Therapeutic Uses/ Current Clinical Trial Indications
Phase II: Generalised Anxiety Disorder
Phase I: Migraine, Headache Disorder, Alcohol Use Disorder and Opioid Use Disorder
Side Effects
Nausea, dizziness, sweating, anxiety, paranoia and delusions, some increase in heart rate and blood pressure
Contraindications (mainly)
History of psychosis
Cardiovascular issues
Safety Profile
Low toxicity
Well-tolerated
Dependence Potential
Low
Tolerance
Rapid development
Drug Interactions
Potentially SSRIs and other serotonergic drugs
5-methoxy-N,N-dimethyltryptamine
(5-MeO-DMT)
Description
5-MeO-DMT is a potent, naturally occurring psychedelic found in certain toads and plants.
Chemical Class
Tryptamine
Mechanism of Action
Most likely mainly 5HT1a
Source
Wide variety of plant species and secreted by the glands of the Colorado River toad
Clinical Trial Doses
Typically: 6mg – 18mg
Route of Administration
Sublingual
Intramuscular
Intranasal
Inhalation
Onset of Action
A few minutes
Duration of Subjective Experience
30-60 minutes
Metabolism
Liver
Monoamine oxidase – A (MAO-A)
Therapeutic Uses/ Current Clinical Trial Indications
Phase II: TRD, Bipolar affective disorder type II depression, Post-partum depression, AUD, Depression/ Anxiety in Alzheimer’s
Phase I: Chronic pain, substance use disorders
Side Effects
Nausea
Vomiting
Non-responsiveness
Intense and immersive experiences
Contraindications (mainly)
History of psychosis
Cardiovascular issues
Safety Profile
Low toxicity
Dependence Potential
Low
Tolerance
Rapid development
Drug Interactions
May interact with SSRIs and other serotonergic drugs
MAO-Inhibitors prolong and intensify the experience and effects of the drug, potentially to a dangerous extent
N,N-Dimethyltryptamine (DMT)
Description
DMT is a powerful, naturally occurring psychedelic compound found in various plants and animals.
Chemical Class
Tryptamine
Mechanism of Action
5HT2a, 2c, 1A and Sigma1
Source
Several plants including Diplopterys cabrerana and Psychotria viridis indigenous to South America
Clinical Trial Doses
Typically: 0.2mg/kg to 0.4mg/kg
Route of Administration
IM
IV
Onset of Action
IM: 5-10 mins
IV: seconds
Duration of Subjective Experience
IM: 30-45 mins
IV: 20-30 mins
Metabolism
Monoamine oxidases
Therapeutic Uses/ Current Clinical Trial Indications
Phase II: GAD, TRD
Phase I: Stroke
Side Effects
Anxiety and intense, transient hallucinations
Contraindications (mainly)
History of psychosis
Cardiovascular issues
Safety Profile
Low toxicity, well-tolerated
Dependence Potential
Low
Tolerance
Rapid development
Drug Interactions
May interact with SSRIs and other serotonergic drugs
MAOIs
Ayahuasca (active ingredient DMT and monoamine oxidase inhibitors)
Description
Ayahuasca is a traditional South American brew made from the Banisteriopsis caapi vine and other plants, containing DMT, used in shamanic rituals for its powerful psychoactive and spiritual effects.
Chemical Class
Tryptamine
Mechanism of Action
5HT2a, 2c, 1A and Sigma1
Source
Several plants including Diplopterys cabrerana and Psychotria viridis indigenous to South America
The above are combined in a brew with Banisteriopsis caapi which contains hamala alkaloids which act as inhibitors of MAO that would otherwise prevent the activity of DMT containing plants when ingested orally
Clinical Trial Doses
Typically:
30-60mg
Route of Administration
Oral
Onset of Action
30-60 mins
Duration of Subjective Experience
4-6 hours
Metabolism
Monoamine oxidases for DMT
Liver for Harmala Alkaloids
Therapeutic Uses/ Current Clinical Trial Indications
Phase I: affective disorders and others
Side Effects
Intense, transient hallucinations, anxiety
Contraindications (mainly)
History of psychosis
Cardiovascular issues
Safety Profile
Low toxicity, well-tolerated
Dependence Potential
Low
Tolerance
Develops with repeated use
Drug Interactions
May interact with SSRIs and other serotonergic drugs
MAOIs
Ketamine
Chemical Class
Arylcyclohexylamine
Mechanism of Action
NMDA antagonism and possible downstream effects on BDNF and mTOR
Source
Synthetic
Clinical Trial Doses
Depends on route of administration but generally in the region of 0.5 -1.0 mg/kg
Route of Administration
IV (more common)
Intranasal (more common)
IM
Oral
Subcutaneous
Sublingual
Onset of Action
Minutes
Duration of Subjective Experience
30-60 minutes
Metabolism
Liver
Therapeutic Uses/ Current Clinical Trial Indications
Licensed: TRD/ MDD
Phase III: Suicidal depression, AUD
Phase II : PTSD
Phase I : Bipolar depression
Side Effects
Dissociation and psychotomimetic effects
Moderate increases in HR and BP
Anxiety
Visual changes
Headache
Nausea
Vomiting
Contraindications (mainly)
Cardiovascular issues
History of substance abuse
History of psychosis
Safety Profile
Low toxicity in controlled settings
Dependence Potential
Moderate
Tolerance
Develops with repeated use
Drug Interactions
CNS depressants
Ibogaine
Description
Ibogaine is a psychoactive compound derived from the root bark of the African shrub Tabernanthe iboga, known for its use in traditional spiritual practices and its potential to interrupt addiction and withdrawal symptoms.
Chemical Class
Substituted Tryptamine/ indole alkaloid
Mechanism of Action
Multiple neurotransmitter sytems
Sigma-2 receptors
NMDA receptors
Kappa opioid receptors
Serotonin and dopamine transporters
Source
Originally the root bark of the iboga tree Tabernanthe iboga in Central Africa
Clinical Trial Doses
Typically: 5-20mg/kg
Route of Administration
Usually oral
Onset of Action
1-3 hours
Duration of Subjective Experience
LONG… 24-72 hours depending on dose and individual metabolism
Metabolism
Liver
Therapeutic Uses/ Current Clinical Trial Indications
Phase I: OUD
Side Effects
Lack of muscle coordination
Nausea
Vomiting
Contraindications (mainly)
Cardiovascular issues (Ibogaine is much more cardiotoxic than other psychedelics)
History of psychosis
Safety Profile
Moderate to high risk due to potential for cardiac toxicity
Dependence Potential
Low
Tolerance
Develops slowly
Drug Interactions
Opioids
SSRIs
Antipsychotics
3,4-Methylenedioxy methamphetamine (MDMA)
Description
MDMA is a synthetic drug known for its empathogenic effects.
Chemical Class
Phenethylamine
Mechanism of Action
VMAT2 inhibition and consequent release of serotonin, noradrenaline and dopamine
5HT2a and c stimulation
Source
Synthetic
Clinical Trial Doses
Typically: 80 – 180mg
Route of Administration
Oral
Onset of Action
30 – 60 mins
Duration of Subjective Experience
3-6 hours
Metabolism
Liver
Therapeutic Uses/ Current Clinical Trial Indications
New drug application (post phase III): PTSD
Phase II: Methylone (a similar drug) for PTSD, MDMA combined with Citalopram for PTSD
Phase I: Autism Spectrum Disorder
Side Effects
Anxiety
Muscle tightness
Sweating
Nausea
Reduced appetite
Contraindications (mainly)
Cardiovascular issues
History of substance abuse
History of psychosis
Safety Profile
Low toxicity at clinical trial doses
Dependence Potential
Moderate
Tolerance
Develops with repeated use
Drug Interactions
SSRIs
MAOIs
Mescaline
Description
Mescaline is a naturally occurring psychedelic alkaloid found in certain cacti, such as peyote.
Chemical Class
Phenethylamine
Mechanism of Action
5HT2a and c
Alpha 1A/ 2A
D1/2/3
Source
Peyote cactus
San Pedro cactus
Clinical Trial Doses
Typically:
Around 300-400mg
Route of Administration
Oral
Onset of Action
45-100 mins
Duration of Subjective Experience
10-12 hours
Metabolism
Liver
Therapeutic Uses/ Current Clinical Trial Indications
Phase I: Obesity, AUD
Side Effects
Nausea
Vomiting
Anxiety
Contraindications (mainly)
History of psychosis
Cardiovascular issues
Safety Profile
Low potential
Dependence Potential
Develops with repeated use
Tolerance
SSRIs
MAOIs
Drug Interactions
SSRIs
MAOIs
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