PSYCHEDELIC

THE LITTLE BOOK OF

SUBSTANCES

PSYCHEDELIC.SUPPORT
 PSILOCYBIN
4-PHOSPHORYLOXY-N,N-DIMETHYLTRYPTAMINE

Psilocybin is a naturally occurring tryptamine alkaloid found in upwards of 200

species of fungi. When consumed, the body rapidly metabolizes psilocybin to

psilocin which activates serotonin 2A (5-HT2A) receptors and profoundly changes

consciousness for 3-6 hours. Psilocybin is a classical psychedelic characterized by

visual distortions, heightened bodily sensations, colorful visions, altered auditory

perceptions, synthesia, strong emotions, hallucinations, and spatial and cognitive

shifts in relation to space and time.

BRAND NAME: none

CHEMICAL NAME:
4-phosphoryloxy-N,N-dimethyltryptamine

DRUG CLASSIFICATION: classic

psychedelic

DRUG TYPE: psilocybin (synthetic),

psilocybin-containing fungi

LEGAL STATUS: illegal in most

countries

CONTROLLED SUBSTANCE (USA):

Schedule I

CLINICAL TRIAL SPONSORS

Usona Institute

COMPASS Pathways

Heffter Institute

Beckley Foundation

University investigator-initiated studies

Many new companies

 PSILOCYBIN
CLINICAL & THERAPEUTICS

Synthetic psilocybin is under investigation in clinical trials in the United States and

Europe for several health conditions. The FDA granted Breakthrough Therapy

designations for psilocybin therapy for both treatment-resistant depression and

major depressive disorder. A Breakthrough Therapy designation can quicken

regulatory approval timelines for novel therapeutics that show better performance

than available medications for life-threatening conditions. Psilocybin clinical trials

are ongoing with FDA marketing approval possible in 2024 or later.

POSITIVE EFFECTS NEGATIVE EFFECTS

Visual distortions Panic attacks, anxiety, or confusion

Vivid imagery with eyes open or Paranoia

closed Dysphoria

Auditory and visual hallucinations Irrational and reckless behavior

Sensory synthesia Impaired concentration and focus,

Feelings of expansiveness disordered thinking

Feelings of oneness and connection Dizziness

with others and the universe Disorientation

Heightened emotions Restlessness

Transcendence of space and time Muscle weakness

Ego dissolution Nausea or vomiting

Mystical experiences Light sensitivity

Altered cognition Pupil dilation

Introspection and insightfulness Flashbacks

4-PHOSPHORYLOXY-N,N-DIMETHYLTRYPTAMINE
 PSILOCYBIN
CLINICAL & THERAPEUTICS

INDICATIONS UNDER STUDY In most countries of the world,

FOR PSILOCYBIN possession and use of psilocybin

mushrooms are illegal. However,

psilocybin retreats are operating

Major depressive disorder
legally in a few countries such as
Treatment-resistant depression
Jamaica and the Netherlands. In
Anxiety and depression in cancer
May 2019, Denver Colorado
patients
became the first US city to
Depression in people with mild
decriminalize psilocybin
cognitive impairment or early
mushrooms followed shortly after
Alzheimer’s disease
by Oakland, Santa Cruz, Ann
Type 2 Bipolar Disorder
Arbor, Washington DC, and the
depression
state of Oregon.
Nicotine dependence

Alcohol use disorder

MECHANISMS
Substance use disorders (cocaine,
OF ACTION
opioid)

Co-occurring depression and High-affinity agonist at serotonin 2A

alcohol use disorder (5-HT2A) receptors, the primary

Cluster, migraine, and post- target for subjective effects

traumatic headache disorders Agonist at 5-HT2C, 5-HT1A, and 5-

Anorexia nervosa HT1B receptors

Obsessive compulsive disorder Modulation of serotonergic,

Demoralization in AIDS/HIV dopaminergic, and glutamatergic

survivors systems

4-PHOSPHORYLOXY-N,N-DIMETHYLTRYPTAMINE
 PSILOCYBIN
CLINICAL & THERAPEUTICS

The psilocybin experience can be metaphorically likened to a journey. During the journey,

the person can visit places deep within the recesses of their own mind, have out-of-body

experiences where they venture to far away universes to meet celestial beings, or even

engage in conversations with loved ones long since passed. The range of possible

experiences is infinite and dose-dependent. A person’s mental state and the environment

where psilocybin is taken affect the subjective and emotional experience.

THERAPEUTIC APPROACH DOSING IN CLINICAL TRIALS

Co-therapy team of two trained Oral (capsule)

guides/therapists deliver the Very low dose (1-9 mg psilocybin)

treatment Low dose (10-19 mg psilocybin)

1 - 4 preparatory sessions Medium dose (20-29 mg psilocybin)

1 - 4 psilocybin sessions, spaced High dose ( >30 mg psilocybin)

weeks to months apart Duration of effects 3-6 hours

Comfortable living room like setting,

participant listens to music and

SAFETY & TOLERABILITY
wears eye shades Well tolerated in individuals

Follow-up integration sessions OR screened for specific

follow-up safety/efficacy physiological and psychological

assessments health criteria

Therapeutic approaches vary widely, Increases or decreases in blood

some include motivational pressure and heart rate

enhancement therapy and various Low potential for dependence in

degrees of psychotherapy while medical and non-medical

others include psychological support settings

with very little Common adverse reactions:

preparation/integration therapy anxiety, psychological distress,

paranoid ideation, physical

discomfort, headache, nausea

4-PHOSPHORYLOXY-N,N-DIMETHYLTRYPTAMINE
PSILOCYBIN
NON-MEDICAL USES

Psilocybin-containing mushrooms have been revered in ceremonial spaces

dating back thousands of years in indigenous cultures, and are still

traditionally used by some indigenous communities in Mexico. With the

discovery of LSD, research into psychedelic compounds and their applications

in psychiatric medicine blossomed. Psilocybin was investigated for

therapeutic benefits throughout the 1960s and gained precedence in Western

cultures when it was popularized among the hippie counterculture. The 1970s

Controlled Substance Act made psilocybin a Schedule I substance where it

resides today.

COMMON STREET NAMES POPULAR

Psilocybin mushrooms or fungi SETTINGS
Magic mushrooms Home

Psychedelic mushrooms Natural environments

Caps Electronic music

Mushies festivals

Shrooms House parties

Fungus Concerts

Buttons Art festivals

Alice

COMMON
ROUTES OF
MUSHROOM
ADMINISTRATION
PREPARATIONS
Oral (dried or fresh
Teas
mushrooms)
Chocolates
Oral (synthetic psilocybin)
Crushed into a powder (edibles
Smoked
or used to fill capsules)

Lemon tek

4-PHOSPHORYLOXY-N,N-DIMETHYLTRYPTAMINE
 PSILOCYBIN
NON-MEDICAL USES

COMMON PSILOCYBIN DOSES*

Microdose: 0.1 - 0.5 grams

Low dose: 0.5 - 2 grams

Moderate dose: 2 - 4 grams

High dose: >4 grams

*Potency varies across different mushroom species

PRIMARY RISKS
Misidentification of

mushrooms

Mushrooms contaminated

with molds or toxins

Physical harms caused by

changes in judgement and

dangerous behaviors

Complications with pre-

existing health conditions

Flashbacks

FACTORS
AFFECTING RISK
PROFILE
Dose

Mushroom sourcing

Pre-existing health

conditions

Set and setting

4-PHOSPHORYLOXY-N,N-DIMETHYLTRYPTAMINE
 MDMA
3,4-METHYLENEDIOXYMETHAMPHETAMINE

MDMA is an amphetamine derivative classified as an entactogen or empathogen.

MDMA induces psychoactive effects of heightened emotions, openness, boundless

love, and feelings of oneness and connection to others and the universe. MDMA

stimulates the release of neurotransmitters (serotonin, dopamine, and

norepinephrine) and hormones (oxytocin, vasopressin, cortisol, and prolactin).

These neurochemicals dynamically interact to induce mind-altering effects and

increase blood pressure, body temperature, and heart rate. MDMA, also known as

Ecstacy and Molly, has been a popular party drug since the early 1980s and is

classified as a Schedule I controlled substance in the US.

BRAND NAME: none

CHEMICAL NAME: 3,4-
methylenedioxymethamphetamine

(MDMA)

DRUG CLASSIFICATION:
empathogen/entactogen

DRUG TYPE: synthetic

LEGAL STATUS: illegal world-wide
CONTROLLED SUBSTANCE (USA):
Schedule I

CLINICAL TRIAL SPONSORS

MAPS / MAPS PBC

MindMed

University investigator-

initiated studies
 MDMA
CLINICAL & THERAPEUTICS

MDMA-assisted psychotherapy is under investigation in clinical trials for treating

several mental health disorders. In a clinical setting with trained therapists, a

person undergoing MDMA treatment is first prepared for the experience in 90-

minute therapy sessions before embarking in all-day MDMA-assisted psychotherapy

sessions (2-3 sessions, spaced 1 month apart). The therapeutic process continues in

follow-up integration sessions where the person reflects on the journey, stabilizes

insights, and establishes a plan for their healing to continue outside the therapy

room.

POSITIVE EFFECTS NEGATIVE EFFECTS

Euphoria Panic attacks, anxiety, or confusion

Heightened awareness and sensory Nausea or vomiting

perceptions Muscle tension, tremors, shaking

Feelings of expansiveness Sweating

Feelings of oneness and connection Blurred vision

with others and the universe Teeth grinding, jaw tightness

Increased energy and alertness Moderate potential for addiction or

Empathy problematic use in non-medical

settings

INDICATIONS UNDER STUDY MECHANISMS

FOR MDMA-ASSISTED OF ACTION
PSYCHOTHERAPY
Posttraumatic stress disorder (PTSD) Binds to and reverses transporter

Anxiety related to a life-threatening proteins (SERT, NET, DAT)

illness Increase release of serotonin,

Social anxiety in autistic adults norepinephrine, and dopamine

Anorexia nervosa Increases release of hormones -

Binge eating disorder oxytocin, vasopressin, prolactin, and

Alcohol use disorder cortisol

3,4-METHYLENEDIOXYMETHAMPHETAMINE
 MDMA
CLINICAL & THERAPEUTICS

In 2017, the FDA granted a

THERAPEUTIC APPROACH (MAPS)
Breakthrough Therapy designation
Co-therapy team of two trained
for MDMA-assisted psychotherapy
health providers deliver the treatment
for the treatment of PTSD.
Three 90-minute preparatory sessions
Preliminary evidence showed
Three 8-hour MDMA-assisted
MDMA was a substantial
psychotherapy sessions, spaced a
improvement over available PTSD
month apart
medications (SSRIs). Clinical trials
Three integration sessions following
are now in the last phase of
each MDMA session
testing (phase 3). If significant,

MDMA could become approved

DOSING IN CLINICAL TRIALS for the treatment of PTSD by

2023.
Oral

Initial dose 75-125 mg MDMA

Supplemental dose equal to half the

initial dose (37.5 - 62.5 mg MDMA)

given two hours later

Duration of effects 6-8 hours

SAFETY & TOLERABILITY

Well tolerated in individuals screened for specific physiological and

psychological health criteria

Increases in blood pressure, heart rate, and body temperature similar to

moderate exercise

Low potential for abuse in medically supervised administrations

Common adverse reactions (reported by >40% in phase 1 MDMA studies):

difficulty concentrating, dizziness, dry mouth, feeling cold, impaired

balance/gait, jaw clenching/tight jaw, lack of appetite, restless legs,

restlessness, and thirst

3,4-METHYLENEDIOXYMETHAMPHETAMINE
 MDMA
NON-MEDICAL USES

COMMON STREET POPULAR ROUTES OF

NAMES SETTINGS ADMINISTRATION
Ecstasy Home Oral (most common)

E, X, and XTC Natural environments Snorted

Molly Nightclubs Rectal

Love drug Electronic music Injected

ADAM festivals Smoked

Beans Raves Pressed tablets, powder,

Disco biscuits Concerts capsules

House parties

Art festivals
ORAL DOSING IN
NON-MEDICAL SETTINGS
Low dose: 60-80 mg

Moderate dose: 81-130 mg

FACTORS AFFECTING
High dose: 131 - 200 mg RISK PROFILE
Very high dose: >200 mg
Dose

Frequency of dosing
PRIMARY RISKS
Contamination of drug source
Dehydration or
or polydrug/medication use
overhydration, both can
Pre-existing disease or health
cause complications when
conditions
a person has taken MDMA
Ambient temperature
Interactions of MDMA with
Activity level
other drugs or medications
Fluid intake
Complications with pre-

existing health conditions

3,4-METHYLENEDIOXYMETHAMPHETAMINE
 KETAMINE
2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE

Discovered in 1962 and patented in 1963, racemic ketamine is an arylcyclohexylamine

used as a rapid-acting general anesthetic agent in human and veterinary medicine.

The FDA approved ketamine in 1970 as an anesthetic drug and is now legally

prescribed off-label for a growing list of indications. Ketamine is a non-competitive

NMDA antagonist and interacts with a number of other receptor targets that

contribute to its effects.

BRAND NAME: Ketalar

CHEMICAL NAME:
2-(2-chlorophenyl)-2-(methylamino)-

cyclohexanone

DRUG CLASSIFICATION: dissociative

DRUG TYPE: synthetic
LEGAL STATUS: legal with a medical
prescription when clinically indicated

CONTROLLED SUBSTANCE (USA):

Schedule III

CLINICAL TRIAL SPONSORS

University investigator-initiated studies

Ketamine Research Foundation

Janssen

DRUG NAME/COMPANY
Ketalar / Par Sterile Products

Ketamine hydrochloride / Mylan Institutional

Ketamine hydrochloride / Hospira

Ketamine hydrochloride / West-Ward Pharms Int

 KETAMINE
CLINICAL & THERAPEUTICS

Beyond its primary application for anesthesia, ketamine is used as an analgesic,

anti-obsessional, and antidepressant compound, and possesses neuroprotective

and neuroplastic properties. The effects of ketamine are highly dependent on the

bioavailable dose by way of the route of administration, ranging from slight

perceptual disruptions to paralysis and full dissociation to sedation. In medical

settings, ketamine is considered relatively safe because it has less circulatory and

respiratory depression compared to other anesthetic agents. Long-term use and

high doses of ketamine are associated with greater incidence of adverse effects

and increased risk of dependence.

POSITIVE EFFECTS ACUTE NEGATIVE EFFECTS

Drowsiness
Anxiety
Dissociative (body dissociates from
Drowsiness
the mind)
Paranoid delusions
Out-of-body experiences
Dysphoria
Changes in perception, cognition,
Distorted perceptions of body and
and emotion
self
Vivid imagery, visual hallucinations
Loss of coordination
Mood enhancement
Disorientation
Ego dissolution
Confusion
Transcendence of space and time
Muscle trembles or jerks
Mystical experiences
Psychotic episodes
Experiences of death and rebirth
Accidents (falling, car, etc)
Muscle relaxation
Psychological distress
Pain relief
Loss of airway function
Feeling of awe and wonder

2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE
 KETAMINE CLINICAL & THERAPEUTICS

NEGATIVE EFFECTS OF Ketamine is only FDA approved for use as

PROLONGED USE an anesthetic agent. However, the last 10

years have brought an increase in off-label

Kidney and bladder (cystitis)
prescriptions for pain management and
toxicity
mental health conditions (major depressive
Urinary tract dysfunction
disorder, OCD, suicidal ideation, and
Physical and psychological
others), meaning rigorous controlled trials to
dependence
gain FDA approval have not been
Misuse, tolerance, and addiction
conducted (except for esketamine, see next
Withdrawal syndrome
section). It's increasingly used to reduce
Flashbacks
depression symptoms and improve mood.
APPROVED INDICATIONS
Some clinicians administer ketamine to

Anesthetic compound for treat PTSD and substance use disorders,

diagnostic and surgical procedures although use for these indications is

experimental and warrants caution.

COMMON OFF-LABEL
Individuals who have substance use
INDICATIONS disorders can be more vulnerable to

Pain become ketamine dependent; those with

Major depression disorder PTSD may have traumatic memories

Mood disorders resurface. Without proper support, these

Addiction disorders* experiences can be harmful rather than

Posttraumatic stress disorder* therapeutic. Research in controlled clinical

*Experimental, caution warranted trials is necessary to establish safety

profiles, dosing, and efficacy for each

MECHANISMS OF ACTION psychiatric indication.

N-methyl-D-aspartate NMDA receptor antagonist (blocks excitatory

signalling of glutamate)

Direct and/or indirect effects at opioid, monoaminergic,

cannabinoid, nitric oxide, muscarinic, nicotinic, and sigma

receptors

Neuroprotective properties, promotes neuroplasticity

2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE
 KETAMINE CLINICAL & THERAPEUTICS

The use of ketamine for mental health DOSING*

symptoms falls into two broad Intravenous (IV)
frameworks - 0.5 mg/kg over a 40 minute infusion

pharmaceutical/biochemical and Dose for Induction of anesthesia: 1.0 -

ketamine-assisted psychotherapy (KAP). 4.5 mg/kg

Ketamine itself has physiological effects Onset of effects 45 seconds (IV)

that appear important for Intramuscular (IM)

antidepressant and other therapeutic For anxiolysis or analgesia:

effects. Some doctors will administer Low dose: 0.25 - 0.5 mg/kg

ketamine, typically through IV infusions Moderate dose: 0.5 - 1.0 mg/kg

or lozenges, to relieve psychiatric To induce psychedelic effects:

symptoms. In this framework, the drug High dose: 1.0 - 2.0 mg/kg

itself acts through neurobiological Dose for Induction of anesthesia: 6.5 -

mechanisms and the symptom relief is 13.0 mg/kg

dependent on repeated administrations Onset of effects 3 mins, Duration of

because the therapeutic effects last for effects 75 mins, sessions last 2-4 hours

days or up to two weeks. Patients are Nasal

offered minimal support and no talk 25-300 mg

therapy which may lead to a Lozenge

dependence on ketamine to achieve Transbuccal and/or sublingual

symptom reduction. Long-term use of absorption

ketamine is associated with negative 50-300 mg

side effects, namely kidney and bladder *Dosing varies depending on route of

toxicity and ketamine tolerance and administration and desired effects

dependence.

ROUTES OF ADMINISTRATION
Oral Subcutaneous

Sublingual/transbuccal Intramuscular (IM)

Intranasal Intravenous (IV)

Rectal Onset and duration of effects dependent on route

2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE
 KETAMINE CLINICAL & THERAPEUTICS

Ketamine-assisted psychotherapy (KAP) is a method where low to moderate doses of

ketamine are delivered with the intention of altering consciousness to facilitate

psychotherapy. A therapist sits and talks with a client as they experience ketamine.

Alternatively, high doses of ketamine are used to induce a non-ordinary state of

consciousness where a person experiences major shifts of perceptions in many ways

similar to classical psychedelics. Mystical-type experiences and feelings of ego

dissolution are common for high dose sessions. These effects can be extremely

negative if a person is not well prepared and supported during and afterwards.

KETAMINE-ASSISTED
SAFETY & TOLERABILITY
PSYCHOTHERAPY
Trained therapeutic provider delivers Well tolerated in individuals

the treatment, qualified medical screened for specific

professionals prescribe ketamine off- physiological and

label psychological health criteria

Preparatory psychotherapy sessions Dose and frequency of use

Ketamine administration session with affects risk profile

psychological support and

psychotherapy during and after

Integration sessions following each

ketamine session

Either immediately after the effects of ketamine dissipate and/or in the days to weeks

to follow, a person undergoes a course of counseling or psychotherapy to examine the

experience and emotions within the framework of their personal goals. The

psychotherapeutic process aims to stabilize positive behavioral changes, consolidate

psychological material, resolve psychological issues, improve relationships, catalyze

new insights, and enhance self-awareness. While still under-researched, ketamine-

assisted psychotherapy is presumed to amplify the neurobiological properties of

ketamine by addressing underlying psychological issues and bolstering

transformational healing.

2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE
 KETAMINE
NON-MEDICAL USES

Similar to other classical psychedelics, not everyone is the right fit for ketamine,

especially at higher doses. Screening for contraindicated medical and mental health

conditions is essential as is a proper setting for psychological safety. Research dating

back to the 1950s and current day psychedelic-assisted clinical trials are elucidating

how psychedelic experiences can be beneficial for therapeutic applications, and what

parameters are necessary to support a person undergoing these experiences.

WANT TO LEARN MORE ABOUT ETHICAL GUIDELINES IN

ADMINISTERING KETAMINE-ASSISTED THERAPY? CHECK OUT
KETAMINE GUIDELINES FOR CLINICIANS AND MORE FROM
KRIYA INSTITUTE.

COMMON STREET POPULAR ROUTES OF

NAMES SETTINGS ADMINISTRATION
Ketamine Nightclubs Nasal

K Discotheques Transbuccal

Special K Raves Sublingual

Kit kat House parties Intravenous

Cat tranquilizer Electronic music Intramuscular

Vitamin K festivals Rectal

Home

2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE
 KETAMINE
NON-MEDICAL USES

DOSING
Dosing and effects are dependent on the route of administration. Ketamine

is administered in liquid or powder form. See clinical section for dosing

examples.

PRIMARY RISKS
Accidents

Misuse, dependence, and addiction

Pre-existing health conditions where a significant elevation of blood pressure

would be hazardous

Impaired memory and mood swings

Flashbacks

Bladder, kidney, and heart toxicity

Sexual assaults

Respiratory depression when mixed with alcohol, GHB, or opioids

*Risks of very high doses: elevated heart rate, hypertension, seizures, coma,

death, stroke, respiratory distress, asphyxiation, and psychological distress

FACTORS AFFECTING
RISK PROFILE
Pre-existing health conditions

Hypersensitivity to ketamine

Duration and frequency of use

Dose

Psychological history

History of trauma

Mixing ketamine with other substances (alcohol and GHB)

2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE
 ESKETAMINE
2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE

BRAND NAME: Spravato

GENERIC NAME: S-ketamine
hydrochloride

CHEMICAL NAME: 2-(2-chlorophenyl)-2-

(methylamino)-cyclohexanone

DRUG CLASSIFICATION:
disassociative

DRUG TYPE: synthetic

LEGAL STATUS: legal with a medical

prescription when clinically indicated

CONTROLLED SUBSTANCE (USA):

Schedule III

SPRAVATO (ESKETAMINE)
Spravato (esketamine)

FDA approved in 2019,

marketed by Janssen

Nasal spray

Must be used in conjunction

with specific oral

antidepressant medications

Common effects: dissociation,

sedation, sleepiness, fainting,

dizziness, spinning sensation,

anxiety, or feeling

disconnected from one’s self,

thoughts, feelings, space and

time
 ESKETAMINE
CLINICAL & THERAPEUTICS

APPROVED RECOMMENDED
INDICATIONS DOSING
For adults with treatment-resistant Initial dose: 56 mg

depression Induction phase (weeks 1 to 4): 56

For depressive symptoms in adults mg or 84 mg administered twice

with major depressive disorder with per week

suicidal thoughts or behaviors Maintenance phase (weeks 5 to 8):

56 mg or 84 mg administered once

TREATMENT DELIVERY weekly administered every 2 weeks

or once per week (week 9 and

Requires patient observation and
after)
monitoring by a healthcare provider
Maintenance phase (week 9 and
for 2 hours after administration
after): 56 mg or 84 mg
Only administered in certified
administered once weekly
medical offices and clinics that
administered every 2 weeks or once
have enrolled in Spravato’s program
per week depending on an
(see REMS)
individual’s response

SAFETY & TOLERABILITY ESKETAMINE CLINICAL TRIAL

Most common adverse reactions of EXCLUSIONS
Spravato plus oral antidepressant: Substance use disorder, active or

dissociation, dizziness, nausea, within the last 6 months

sedation, vertigo, hypoesthesia, Current or past psychosis

anxiety, lethargy, blood pressure Bipolar disorder

increased, vomiting, feeling drunk,

euphoric mood, and vertigo

2-(2-CHLOROPHENYL)-2-(METHYLAMINO)-CYCLOHEXANONE
PSYCHEDELIC.SUPPORT
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AYAHUASCA
N,N-DIMETHYLTRYPTAMINE (DMT)

Ayahuasca is a mixture of at least two types of plants, most commonly Psychotria viridis

and Banisteriopsis caapi, that contain N,N-dimethyltryptamine (DMT) and monoamine

oxidase inhibitors (MAOI). Originating in the Amazon basin, its use in shamanic

ceremonies for spiritual and medicinal purposes dates back centuries. The word

“ayahuasca” is Quechua and translates as “the vine or rope of the dead”. To this day,

many indigenous peoples uphold the tradition in their cultures, and it is also used

sacramentally by a number of organized religions. Interest by Western societies has

steadily increased over the last few decades because of its purported capacity to heal

intractable diseases and exert positive effects on health and wellbeing.

BRAND NAME: none

CHEMICAL NAME: N,N-dimethyltryptamine (DMT)

and harmala alkaloids [7-Methoxy-1-methyl-9H-

pyrido[3,4-b]indole (harmine); 4,9-Dihydro-7-

methoxy-1-methyl-3H-pyrido[3,4-b]indole

(harmaline); 1,2,3,4-tetrahydro-harmine

(tetrahydroharmine)]

DRUG CLASSIFICATION: psychedelic

DRUG TYPE: plant mixture
LEGAL STATUS: legal in some Central and South

American countries; illegal in the USA except for

legal religious exemption for specific churches in

the USA; decriminalized in many countries

CONTROLLED SUBSTANCE (USA): Schedule I

CLINICAL TRIAL SPONSORS

Sacred Medicines Public

Benefit Corporation

University investigator-

initiated studies
AYAHUASCA
CLINICAL & THERAPEUTICS

The therapeutic potential of ayahuasca in the treatment of mood disorders,

posttraumatic stress disorder and substance use disorders, is currently under

investigation in a small number of clinical trials and surveys. The first randomized

placebo-controlled trial of ayahuasca for treatment-refractory depression

demonstrated robust and rapid antidepressant effects from a single dose of

ayahuasca when compared to placebo. Another study using data from the Global

Drug Survey suggests that the rates of alcoholism were lower in ayahuasca users

when compared to people that used LSD or mushrooms.

POSITIVE EFFECTS NEGATIVE EFFECTS

Visual distortions Panic attacks, anxiety, or confusion

Vivid imagery with eyes open or Nausea or vomiting

closed Diarrhea

Purging (physical and emotional) Psychological distress

Auditory and visual hallucinations Physical discomfort

Feelings of expansiveness Impaired concentration and focus,

Feelings of oneness and connection disordered thinking

with others and the universe Dizziness

Heightened emotions Disorientation

Transcendence of space and time Muscle weakness or tension

Ego dissolution Muscle spasms

Mystical and spiritual experiences Light sensitivity

Altered cognition Pupil dilation

Introspection and insightfulness Body temperature fluctuations

Euphoria Dysphoria

Physical sensations Paranoia

Delusions

Seizures (rare)

N,N-DIMETHYLTRYPTAMINE (DMT)
AYAHUASCA CLINICAL & THERAPEUTICS

INDICATIONS UNDER STUDY Hearing of the potential of

FOR AYAHUASCA OR DMT ayahuasca to treat mental health

conditions, a growing number of

Treatment-resistant depression
individuals are seeking out
Phase 1 healthy individuals (safety
ayahuasca at retreat centers in
trial for DMT)
Central and South America,

church ceremonies, and

MECHANISMS
underground community circles.
OF ACTION
Before partaking, people usually

Harmala alkaloids inhibit MAO in the follow a special diet, called a

gut allowing DMT to reach the brain ‘dieta’ in traditional practices, to

Potent partial agonist at serotonin cleanse and prepare the body for

2A (5-HT2A) receptors, the primary upcoming ayahuasca experiences.

target for subjective effects; Typically, gatherings last for a

agonist at other 5-HT subtypes weekend or up to a few weeks,

Sigma-1 receptor agonist with multiple occasions where

TAAR-1 agonist ayahuasca is consumed

Modulation of glutamatergic system

Ayahuasca induces non-ordinary states of consciousness where a person may

experience visionary states, alterations in mood and perceptions, and physical and

emotional purging. In traditional lineages, music and singing of special songs

called Icaros are predominant features of the ritual, and many who practice with

ayahuasca carry and pass down these ways of working with the medicine. The

journeyer is supported by these healing songs if physical (vomiting, diarrhea,

shaking) and emotional purging comes, or as they transverse their deepest inner

worlds. After drinking ayahuasca, it's a common practice for groups to meet the

following morning to share and process the experience with others in integration

circles. Many keep the diet in place for at least 3-7 days to solidify the effects of

the plant medicine and further reflect on the meaning and insights brought into

conscious awareness.

N,N-DIMETHYLTRYPTAMINE (DMT)
AYAHUASCA CLINICAL & THERAPEUTICS

Recent neuroscience research THERAPEUTIC APPROACH

suggests the active components of Supportive therapy and integration

ayahuasca can induce sessions

neuroplasticity and the generation Group administrations (planned)

of new neurons. Although this has

not been demonstrated in human

DOSING OF DMT IN
brains, these findings lend support CLINICAL TRIALS
to a neurobiological underpinning 54 mg, 69 mg, 90 mg, 115 mg (IV)

for the changes in thought patterns

DOSING OF AYAHUASCA IN
and behaviors ayahuasca drinkers

report. This isn’t to say the

CLINICAL TRIALS
psychospiritual aspects of the 0.36 mg/kg DMT (Palhano-Fontes,

experience aren’t necessary or 2017)

important, but describes how Duration of effects: 4 hours

neural pathways may adapt to SAFETY & TOLERABILITY

allow for new ways of seeing and Non-toxic

being in the world. Drug interactions can be

serious
Pharmaceutical sponsors are
Severe psychological distress
interested in taking ayahuasca
or psychotic breaks can occur
through the FDA development

path with hopeful approval. While not identical in effects to the plant-based

Developing botanical drugs is brews, a synthetic version is available and could be a

challenging, only two have ever drug studied for medical use. DMT administrations

become FDA-approved, and through routes other than oral ingestion are another

many who use ayahuasca as a method underdevelopment and could be regulated

sacrament question its place in as medicines. To mimic ayahuasca, a new trial will

modern medical practices, examine slow IV administrations of DMT to prolong

particularly if profit motives are the effects and maintain steady levels of DMT in the

predominant. ‘Pharmahuasca’ blood. Otherwise, the duration of effects is only

refers to a synthetic mixture of about 15 minutes for smoked or single injections of

DMT and harmala alkaloids. DMT.

N,N-DIMETHYLTRYPTAMINE (DMT)
 AYAHUASCA
NON-MEDICAL USES

Indigenous peoples of the Amazon discovered ayahuasca and passed down the sacred

knowledge of these practices for many generations. Only in the 1950s did a few Westerners

really catch on to the healing properties and take interest in partaking in ayahuasca

ceremonies. Since then there has been a boom of ‘ayahuasca tourism’ where people from

all over the globe are trekking to retreat centers in Central and South America. The plants

are exported out of the jungles of the Amazon to be served at underground gatherings

across the world. This blossoming interest and resulting over harvesting of ayahuasca

threatens the sustainability of the plants and the cultures who hold plant medicines as

central tenants in their cosmologies. Conservation of the plants and their natural

ecosystems, and reciprocity to the indigenous peoples who shared their long-held wisdom

of the plants, must be paramount as psychedelics come into the focus of mainstream global

culture.

COMMON STREET POPULAR

NAMES SETTINGS
Malocas
Huasca
Yurts
Yajé
Ceremonies and
Caapi
rituals
Daime
Natural environments
Vegetal
Living rooms
Grandmother plant

Spirit molecule

ROUTES OF COMMON
ADMINISTRATION PREPARATIONS
Oral (plant brew) Banisteriopsis caapi

Oral (freeze dried capsules Psychotria viridis

of plants) Over 100 other plants

Smoked (DMT) documented

Intravenous (DMT)

Intramuscular (DMT)

N,N-DIMETHYLTRYPTAMINE (DMT)
AYAHUASCA
NON-MEDICAL USES

AYAHUASCA DOSES* FACTORS AFFECTING

Analysis of ayahuasca from several RISK PROFILE
sources by Callaway:
Dose
DMT concentration: between 0.16
Drug/medication interactions
mg/mL and 14.15 mg/mL (although
Pre-existing health conditions
some samples did not contain any
Set and setting
DMT)

THH concentration: between 0.49

mg/mL and 23.80 mg/mL

Harmaline concentration: between 0.01

mg/mL and 0.9 mg/mL

Harmine concentration: between 0.45

mg/mL and 22.85 mg/mL

Doses vary across traditions between

20-200 mL

*Potency varies across brews made from

various plants

PRIMARY RISKS
Other plants added to the

mixture

Complications with pre-

existing health conditions

Drug interactions with

contraindicated

medications

Sexual assaults

Vulnerable states;

misjudgements

Psychological distress

N,N-DIMETHYLTRYPTAMINE (DMT)
5-MeO-DMT
5-METHOXY-N,N-DIMETHYLTRYPTAMINE

A tryptamine derivative, 5-MeO-DMT is a very strong, fast-acting psychedelic

compound with a short duration. The effects include vision and auditory

alterations, out-of-body experiences and mystical type experiences, but unlike

other classical psychedelics the visionary effect is often eclipsed by the emotional

impact of the experience. 5-MeO-DMT has a different chemical structure and

effect profile from N,N-DMT (compound in ayahuasca), and is considered more

intense and powerful.

BRAND NAME: none

CHEMICAL NAME: 5-methoxy-N,N-
dimethyltryptamine

DRUG CLASSIFICATION:
empathogen/entactogen

DRUG TYPE: classical psychedelic

LEGAL STATUS: illegal the US; other
countries it is unscheduled and

unregulated (i.e. Mexico)

CONTROLLED SUBSTANCE (USA):

Schedule I

CLINICAL TRIAL SPONSORS

GH Research Limited

Beckley PsyTech

Usona Institute
5-MeO-DMT
CLINICAL & THERAPEUTICS

5-MeO-DMT can be extracted from specific plant species or from the venom of the

Incilius alvarius toad (aka, Bufo alvarius, Sonoran Desert or Colorado River toad). The

bufotoxin venom contains 5-MeO-DMT and bufotenine, both psychoactive substances.

A full dose (50 mg) of vaporized bufotoxin consists of approximately 10-15% of 5-MeO-

DMT and induces mystical type-experiences of similar intensity to high-dose psilocybin

(30 mg/70 kg). The duration of effects depends on the route of administration but for

smoked 5-MeO-DMT effects are typically felt 0-30 seconds after ingestion, peak

around 15 minutes, and dissipate 30 minutes after administration.

POSITIVE EFFECTS NEGATIVE EFFECTS

Euphoria Nausea or vomiting

Changes in bodily sensations Anxiety

Out of body experiences Confusion, delusion

Increased or decreased visual Pupil dilation

acuity Loss of motor control, spastic

Unity and interconnectedness movements

Perception of infinity Tremors, muscle spasms

Time distortion Respiratory depression

Catharsis Skin flushing

Ego dissolution Disorientation

Bliss Temperature regulation suppression

Spiritual experiences

Auditory distortions or
MECHANISMS OF ACTION
hallucinations
Non-selective agonist at serotonin

receptors (5-HT2A, 5-HT2C, 5-HT1A)

INDICATIONS UNDER STUDY
Bufotenine (metabolite of 5-MeO-DMT
FOR 5-MeO-DMT
and often co-occurring compound in
Treatment-resistant depression
plants and toad) - high affinity 5-HT2A

receptor agonist

Acts at many glutamate, dopamine, and

acetylcholine receptors

5-METHOXY-N,N-DIMETHYLTRYPTAMINE
5-MeO-DMT
CLINICAL & THERAPEUTICS

Some suspect 5-MeO-DMT

THERAPEUTIC APPROACH (MAPS)
containing toad venom was used
Supportive therapy and integration
by ancient civilizations in
care
shamanic healing ceremonies, but
New clinical approaches under
conclusive evidence is lacking.
development
Dating back to the late 8th

century, some snuffs of South

LABORATORY DOSING American indigenous tribes were

Duration of effects 15 to 90 minutes found to contain 5-MeO-DMT. It

Inhalation (~6 to 12 mg) was first synthesized in 1936, only

IV (~0.7 to 3.1 mg) to become known to a small

Sublingual or intranasal (~10 mg) number of people in the 1970s. It's

expanding popularity over the

SAFETY & TOLERABILITY decades, and its commercial

distribution through mail orders,

Data from controlled clinical trials
prompted its placement on the
unavailable
Schedule I list of controlled
Low potential for dependence in
substances in 2011.
medical and non-medical settings

5-MeO-DMT can be easily synthesized in a laboratory, as demonstrated here by

Hamilton Morris. While some advocates argue that the constituents of bufotoxin

might have synergistic effects, the threat of over harvesting venom from toads

and the impact on local communities in the Sonoran desert is a growing concern.

Synthetic 5-MeO-DMT is an alternative that can alleviate peril of the toads and

their natural habitats. Synthetic drugs allow for much more precise dosing which

is paramount for a drug as potent as 5-MeO-DMT. Drug development sponsors

are now making a synthetic version to test for treating mental health conditions

after anecdotal reports of 5-MeO-DMT bringing relief for depression, anxiety,

substance use, and mood disorders.

5-METHOXY-N,N-DIMETHYLTRYPTAMINE
5-MeO-DMT
NON-MEDICAL USES

COMMON POPULAR ROUTES OF

STREET NAMES SETTINGS ADMINISTRATION
5-MeO Home Inhalation (smoked)*

Toad medicine Natural environments IV

Sonoran toad Ceremonies Sublingual

Colorado river toad Therapeutic settings Intranasal (snorted)

venom Rectal

Bufo

God molecule

Yopo

SMOKED TOAD VENOM COMMON APPEARANCES

DOSAGE (AT LEAST 10% Dried toad venom (tan crystals)

IS 5-MEO-DMT)
*Synthetic and toad forms differ in terms
Threshold 10-20 mg
of dosing and route of administration. Toad
Moderate 20-50 mg
venom can only be administered through
Common 50-70 mg
vaporization because of other chemicals
Strong 70-100 mg
present in the venom.

PRIMARY RISKS FACTORS AFFECTING

Unknown or imprecise dosing can RISK PROFILE
lead to acute and prolonged
Dose
adverse effects
Pre-existing health conditions
Complications with pre-existing
Set and setting
health conditions
Psychological preparation
Unskilled guides and facilitators

Psychological distress/spiritual

emergency

5-METHOXY-N,N-DIMETHYLTRYPTAMINE
 LSD
LYSERGIC ACID DIETHYLAMIDE

One of the most well known classical psychedelics, lysergic acid diethylamide aka

LSD, came into this world through an accidental discovery by the chemist Albert

Hoffman on April 19, 1943. He first made LSD-25 in 1938 but didn’t become aware

of the mind-shifting properties until he unknowingly absorbed a dose in the

laboratory and felt the full effects in a harrowing bicycle ride home. The profound

trip led to a quest by his employer Sandoz Laboratories to find out how this

substance could be used in clinical applications. They distributed LSD to doctors

and therapists around the world to administer to their patients and themselves in

hopes of finding a medical use.

BRAND NAME: Delysid (1950-60s)

CHEMICAL NAME: lysergic acid
diethylamide

DRUG CLASSIFICATION: classical

psychedelic

DRUG TYPE: synthetic

LEGAL STATUS: illegal
CONTROLLED SUBSTANCE (USA):
Schedule I

CLINICAL TRIAL SPONSORS

Mind Medicine

MAPS

Beckley Foundation

Investigator-initiated studies
 LSD
CLINICAL & THERAPEUTICS

The research lasted for a few decades and amassed reports of therapeutic value

for a wide range of mental health conditions. But by the mid-1960s, the drug had

gained popularity outside of clinical settings and became associated with the

counterculture, anti-war agenda, and hippie movement. In 1970, the Controlled

Substance Act was passed into law, placing LSD and other psychedelics in the

most restrictive class - Substance I Controlled Substances. LSD research was shut

down and the possession and use of LSD was criminalized with the highest

penalties for offenders.

POSITIVE EFFECTS NEGATIVE EFFECTS

Visual distortions Panic attacks, anxiety, or confusion

Vivid imagery with eyes open or Paranoia

closed Dysphoria

Auditory and visual hallucinations Irrational and reckless behavior

Sensory synesthesia Impaired concentration and focus,

Feelings of expansiveness disordered thinking

Feelings of oneness and connection Dizziness

with others and the universe Disorientation

Heightened emotions Restlessness

Transcendence of space and time Weakness

Ego dissolution Numbness

Mystical experiences Nausea or vomiting

Altered cognition Light sensitivity

Introspection and insightfulness Pupil dilation

Flashbacks
INDICATIONS UNDER STUDY Tremors

FOR LSD Perspiration

Pain management

ADHD

Anxiety related to a life-threatening

illness

LYSERGIC ACID DIETHYLAMIDE

 LSD
CLINICAL & THERAPEUTICS

MECHANISMS Research came to a screeching

OF ACTION halt, but LSD did not disappear - it

High-affinity agonist at serotonin 2A went underground. According to a

(5-HT2A) receptor, the primary 2017 report, an estimated 10% of

target for subjective effects individuals in the US have used

Agonist at most serotonin receptors LSD in the past and 0.7% had

subtypes 5-HT1A, 5-HT2B, 5-HT2C, taken it in the last year

5-HT5A, 5-HT6; agonist at dopamine (drugabuse.org). From 2015 to

(D2) receptors 2018, LSD consumption by US

Modulation of serotonergic, adults increased 56.4%.

dopaminergic, and glutamatergic

systems
SAFETY & TOLERABILITY
Well tolerated in individuals
THERAPEUTIC APPROACH
screened for specific
Microdose protocols (very low dose
physiological and
repeated every few days)
psychological health criteria
LSD-assisted psychotherapy
Low potential for dependence

THERAPEUTIC DOSING in medical and non-medical

settings
Oral

Very low doses: 5, 10, 20 µg Common adverse reactions in a

Typical dose: 100 µg trial: illusion, anxiety, emotional

200 µ g
distress, feeling abnormal,
Medium dose:
feeling cold
Duration of effects 6 to 12 hours

LSD is a potent substance for altering consciousness. The dosage is in micrograms ( µg) - a
tiny amount compared to most other drugs - and the duration of effects is long (anywhere

from 6 to 12 hours). Now over 50 years since it was banned, LSD is once again under study

in clinical trials. The first publication of modern-era LSD research reported significant

benefits for people coping with anxiety associated with life-threatening illnesses. Other

studies are interested in how LSD microdosing (tiny sub-perceptual, repeated doses) can

affect pain severity or ADHD symptoms.

LYSERGIC ACID DIETHYLAMIDE

 LSD
NON-MEDICAL USES

COMMON STREET POPULAR ROUTES OF

NAMES SETTINGS ADMINISTRATION
Acid Home Oral

L Natural environments Subcutaneous

Cid Electronic music

Lucy festivals
COMMON
Dots House parties
APPEARANCES
Mellow yellow Concerts Liquid drops

Window pane Art festivals Blotter paper

Blotter Therapeutic settings Tablets (microdots) or

Orange sunshine capsules

Candy

Patch (for skin)

As with all psychedelics, the environment and

person’s psychological state can dramatically

impact the LSD experience. Not everyone is a

LSD DOSES
suitable candidate for taking LSD, particularly Microdose: 5 - 19 µg
those with a background or family history of Low dose: 20 - 75 µ g

psychotic disorders (schizophrenia, bipolar Moderate dose: 76 - 200 µg

disorder, etc). Caution and harm reduction High dose: 201 - 400 µg
practices are essential for safe use. Very high dose: >400 µ g

PRIMARY RISKS FACTORS AFFECTING

Physical harms caused by changes RISK PROFILE
in judgement and dangerous
Dose
behaviors
Pre-existing health conditions
Complications with pre-existing
Set and setting
health conditions

Flashbacks

LYSERGIC ACID DIETHYLAMIDE

 CANNABIS
Δ9-TETRAHYDROCANNABINOL (THC), CANNABIDIOL (CBD)

Cannabis is a flowering herb in the plant family Cannabaceae. The plant has been

used for medicinal and industrial purposes for thousands of years by many cultures

across the globe. It contains at least 113 naturally occurring chemical compounds

called cannabinoids. Some cannabis varieties contain a psychoactive cannabinoid

called tetrahydrocannabinol (THC) that induces a range of subjective effects

dependent on the dose. Another cannabinoid named cannabidiol (CBD) does not

cause intoxication but is used for health benefits. The flowers of Cannabis sativa

and Cannabis indica are smoked, vaporized, eaten, or topically applied for

recreational and medicinal purposes. Cannabis plants cultivated for industrial (no

THC, non-drug) use are referred to as hemp and have many uses when processed

for textiles, paper, health foods, building materials, and biodegradable plastics.

BRAND NAME: Epidiolex (cannabidiol),

Marinol (dronabinol), Syndros

(dronabinol), and Cesamet (nabilone)

CHEMICAL NAME: Δ9-

tetrahydrocannabinol (THC), cannabidiol

(CBD)

DRUG CLASSIFICATION: endocannabinoids

DRUG TYPE: THC/CBD (synthetic), cannabis plants
LEGAL STATUS: mixed in US (legal with prescription,
legal in some US states, decriminalized in some

states, US federally illegal); varies world-wide

CONTROLLED SUBSTANCE (USA): Schedule I

(THC/CBD/cannabis plants)

CLINICAL TRIAL SPONSORS

Pharmaceutical companies

University investigator-

initiated studies
 CANNABIS
CLINICAL & THERAPEUTICS
According to the United States federal government, cannabis remains illegal as Schedule

I Controlled Substance. However, at least 18 states and the District of Columbia have fully

legalized cannabis use and the majority of the other states have either legalized medical

cannabis use and/or decriminalized personal use.

The FDA has not approved cannabis for the treatment of any health conditions but has

approved Epidiolex (cannabidiol), a cannabis-derived drug product, and three synthetic

cannabis-related drug products - Marinol (dronabinol), Syndros (dronabinol), and

Cesamet (nabilone). The proclaimed therapeutic effects of cannabis span many

conditions but the largest amount of evidence from research supports the benefits of

cannabis for pain reduction, nausea and vomiting induced by chemotherapy, and muscle

spasticity in multiple sclerosis.

POSITIVE EFFECTS NEGATIVE EFFECTS

Paranoia, anxiety, panic, and
Changes in sensory perceptions
psychosis
Elevated mood
Dry mouth
Alterations in sense of time
Disorientation
Relaxation
Delusions and hallucinations (high
Euphoria
doses)
Increase in sociability
Increased heart rate
Heightened creativity
Difficulty thinking clearly

COMMON INDICATIONS FOR Altered judgement

MEDICAL CANNABIS Loss of coordination

Pain NEGATIVE EFFECTS OF

Posttraumatic stress disorder
PROLONGED USE
Epilepsy
Brain fog
Cancer and symptoms related to
Breathing problems
treatments
Dependence
Neurodegenerative diseases
Impaired memory, concentration, and

problem-solving

Fertility issues

Δ9-TETRAHYDROCANNABINOL (THC), CANNABIDIOL (CBD)

 CANNABIS
CLINICAL & THERAPEUTICS

Although not backed by substantial scientific evidence, people self-medicate with

cannabis and CBD to reduce anxiety and depression symptoms, improve sleep

quality, manage stress, and mitigate PTSD symptoms. However, some research has

found that heavy use of high-potency cannabis can be associated with adverse

mental health consequences, increased risk for worsening of psychiatric symptoms

and substance use disorders, and imparied learning and memory.

MECHANISMS PREPARATIONS AND

OF ACTION APPROACHES
Whole plant preparations
THC: activation of cannabinoid CB1
Edibles
receptors
Tinctures
CBD: antagonist of GPR55
Topicals
receptors; inverse agonist of GPR3,
Cannabis-assisted psychotherapy
GPR6, and GPR12; allosteric

modulator of opioid receptors;

CANNABIS DISPENSARIES
PPAR 𝞬 agonism; inhibition of
Located in states permitting
voltage-gated cation channels;
medical or recreational cannabis
intracellular calcium release
Doctor issued medical cannabis

BRAND NAME (GENERIC) / license required in some states

PHARMACEUTICAL COMPANY Carry a variety of cannabis flowers,

Cannabis-derived drug tinctures (oils), edibles, topicals,

Epidiolex (cannabidiol) / GW and cannabis-related merchandize

Pharmaceuticals Bud tenders or medical

Synthetic cannabis-related drugs consultation available for advice

Marinol and Syndros (dronabinol) / on cannabis products.

Solvay Pharmaceuticals, PAR

Pharmaceutical Companies, Alkem Labs

Cesamet (nabilone) / Eli Lilly and

Company, Valeant Pharmaceuticals

Δ9-TETRAHYDROCANNABINOL (THC), CANNABIDIOL (CBD)

 CANNABIS CLINICAL & THERAPEUTICS

DOSING Cannabis-assisted psychotherapy

is an approach where a person

Dosing and frequency of
consumes cannabis with the
administration varies widely. Duration
intention of exploring emotions,
of effects depends on the route of
thoughts and sensations under the
administration.
guidance of a therapist. Under the

relaxing effects of cannabis, a

SAFETY & TOLERABILITY person may more easily approach

Low physiological toxicity, no and work with difficult emotions

lethal overdoses from a different self view point.

Well tolerated in individuals This technique is relatively novel

without pre-existing psychotic and encompasses other

disorders therapeutic practices such as

Challenging psychological breathing and relaxation

experiences can occur exercises. Cannabis-assisted

Adverse effects associated with psychotherapy is only available in

duration and amount of use states where cannabis is legal.

Δ9-TETRAHYDROCANNABINOL (THC), CANNABIDIOL (CBD)

 CANNABIS
NON-MEDICAL USES

COMMON STREET POPULAR ROUTES OF

NAMES SETTINGS ADMINISTRATION
Cannabis Home Inhaled (smoked)

Marijuna Outdoor environments Joints

Weed Spiritual practices Pipes

Herb Hikes Bongs

THC House parties Blunts

CBD Electronic music Inhaled (vaporized)

festivals Oral

Edibles

Drinks

Capsules

Tinctures (oils)

FACTORS AFFECTING
DOSING RISK PROFILE
Dosing and frequency of
Pre-existing health conditions
administration varies widely. Duration
Dosage
of effects depends on the route of
Environment
administration.
Duration of use

PRIMARY RISKS
Anxiety, panic attacks, or paranoia

Memory and problem-solving impairment

Misuse, dependence, and addiction

Increased risk of psychosis or worsening of schizophrenia symptoms

in those at high genetic risk

Δ9-TETRAHYDROCANNABINOL (THC), CANNABIDIOL (CBD)

 IBOGAINE
12-METHOXYIBOGAMINE

Iboga refers to perennial rainforest shrubs in the Apocynaceae family, including

the most well known species Tabernanthe iboga. Customarily used in shamanic

healing and initiation ceremonies of Central African traditions, iboga is a plant

with roots and bark containing the psychoactive alkaloid ibogaine. People of

Gabon have practiced with iboga as a sacrament in their Bwiti religion for

hundreds of years. Through passed down knowledge accumulated over thousands

of years, providers of iboga are extensively trained to work with this plant

medicine in West African traditions.

BRAND NAME: none

CHEMICAL NAME: 12-methoxyibogamine

DRUG CLASSIFICATION: plant

mixture

DRUG TYPE: plant derived

LEGAL STATUS: illegal or restricted
in most countries; unscheduled in

Mexico and West Africa

CONTROLLED SUBSTANCE (USA):

Schedule I

CLINICAL TRIAL SPONSORS

University investigator-

initiated studies

MAPS

Sacred Medicines Public

Benefit Corporation

New pharmaceutical

companies
 IBOGAINE
CLINICAL & THERAPEUTICS

Ibogaine became known as a helpful tool for reducing opioid withdrawal and

craving in 1962 after Howard Lotsof accidentally discovered the anti-addictive

effects after ingesting ibogaine. It has also been shown to reverse addiction to

stimulants, alcohol, and nicotine. Preclinical research and phase 1 clinical studies

were conducted in the early 1990s to evaluate the safety of ibogaine, but the

studies were ended due to intellectual property disputes and a death associated

with ibogaine outside of medical contexts. Currently, it is not approved for the

treatment of addiction or any other medical conditions.

POSITIVE EFFECTS NEGATIVE EFFECTS

(HIGHER DOSES) Loss of coordination

Dream-like state Nausea

Vivid imagery with eyes closed Vomiting

Hallucinations and visual distortions Sensitivity to light and sounds

Memory recall Pupil dilation

Introspection Dizziness

Conceptual thinking Tremors

Anxiety

POSITIVE EFFECTS Delusions

(LOWER DOSES) Mania or psychosis

Increased energy Dehydration/loss of electrolytes

Stimulant effects Seizures*

Lack of appetite Irregular heartbeat

Increased blood pressure

Cardiac arrest

Death from acute heart failure or

cardiopulmonary arrest

*Related to acute alcohol or

benzodiazepine withdrawal

12-METHOXYIBOGAMINE
 IBOGAINE
CLINICAL & THERAPEUTICS

Observational studies and case reports show ibogaine can reduce drug craving

and withdrawal symptoms, and some individuals had sustained reductions of opioid

use 12 months after undergoing ibogaine treatment. Research in animal models

report ibogaine to reduce consumption of alcohol, stimulants, and opioids.

INDICATIONS UNDER STUDY MECHANISMS

FOR IBOGAINE OF ACTION
Alcohol use disorders Potent serotonin reuptake inhibitor

Methadone detoxification Κ -opioid receptor agonist

Opioid use disorders μ -opioid receptor agonist and

TBI partial agonist (weak)

Sigma-2 receptor agonist

Inhibits nicotinic acetylcholine

receptors and NMDA receptors

Modulates many other

neurotransmitter systems

Ibogaine clinics operate in Mexico because people can use and possess ibogaine

but it is still illegal to use it as a medicine because it is not scheduled or regulated.

Ibogaine is illegal or restricted in many countries including the USA (Schedule I

substance). With the resurgence in psychedelic research, there is renewed interest

in controlled evaluation of ibogaine. A phase 2 trial in Brazil is investigating

ibogaine for the treatment of alcohol use disorders; a phase 2 trial in Spain is

testing ibogaine for methadone detoxification. Other companies have announced

plans to conduct ibogaine research for opioid use disorders.

12-METHOXYIBOGAMINE
 IBOGAINE CLINICAL & THERAPEUTICS

The ibogaine experience typically

THERAPEUTIC APPROACHES progresses through a visionary

phase (4 to 8 hours), an
Ibogaine administration under
introspection phase (8 to 20
medical supervision
hours), and finally a stimulatory
Integration and recovery support
phase (24 to 72 hours).

THERAPEUTIC DOSING OF Unlike most psychedelic

IBOGAINE HCL substances, ibogaine is associated

with serious adverse effects, and

100 mg
even death. Fatalities are usually
Ascending doses (100 to 600 mg)
attributed to other factors such as
240 mg
pre-existing medical conditions,
240 mg, 320 mg
mostly related to cardiovascular
240 mg, 320 mg, 400 mg
dysfunction, and contraindicated

medications or drugs.

SAFETY & TOLERABILITY For these reasons, medical

Individuals must be screened for screening (ECG/EKG, liver panel,

cardiovascular conditions and review of medical conditions) and

other pre-existing health discontinuation of contraindicated

conditions drugs prior to taking ibogaine is

Contraindicated medications and extremely important. Ibogaine

drugs must discontinued should never be taken alone;

Low potential for dependence in administrations should be under

medical and non-medical settings medical supervision with an

Trials ongoing - tolerability data automated external defibrillator

unavailable (AED) onsite.

12-METHOXYIBOGAMINE
 IBOGAINE
NON-MEDICAL USES
Synthetic ibogaine is not widely available because the process to make it is difficult and

has yet to be optimized. Iboga plants are grown to source ibogaine. As interest in this

plant medicine grows, people must be conscientious of the impacts on the indigenous

people who traditionally use iboga and the sustainability of the plants.

COMMON STREET POPULAR ROUTES OF

NAMES SETTINGS ADMINISTRATION
Iboga Ceremonies Oral

Ibogaine Initiation rites (Bwiti, Iboga root (chewed)

Eboga Central African Ibogaine (extracted alkaloid)

Endabuse traditions)

Tabernanthe iboga Clinics

DOSES (ORAL) FOR COMMON

IBOGAINE HYDROCHLORIDE APPEARANCE
2-3 mg/kg (test dose to check for Iboga root

allergic reaction) Brown powder in capsules

6-20 mg/kg (single ‘flood dose’)

1-5 mg/kg (booster dose) PRIMARY RISKS

Dosing should never exceed 24 mg/kg Severe adverse effects or death

in 24 hours from underlying cardiac

25 mg (Microdosing) conditions

Complications with pre-existing

DOSES (ORAL) IBOGA ROOT BARK health conditions
5-100 grams
Interactions with other drugs or

FACTORS AFFECTING medications

RISK PROFILE Psychological distress

Dose (>12 mg/kg increase risk for cardiac abnormalities)

Pre-existing health conditions

Contraindicated drugs and medications (including opioid drugs)

Set and setting

12-METHOXYIBOGAMINE
PSYCHEDELIC
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