Psychedelics 101

Comprehensive information on the most common psychedelics and related compounds.

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 at serotonin and dopamine receptors: 5-HT1a, 2a, 2b, 2c, 5a and 6 mainly, with 5HT2a activity and possibly D2 being mainly 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

Intense, transient hallucinations, anxiety 

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