Psychedelics & Cannabinoids

Question 1

List the Psychedelics & Cannabinoids

Answer 1

Dimethyltryptamine (DMT)/Ayahuasca
Lysergic Acid diethylamide
3,4-Methylenedioxymethamphetamine (MDMA)
Mescaline/Peyote
Psilocybin
Tetrahydrocannabinol/Cannabis

Question 2

Describe the major psychological effects of psychedelic drugs, including the importance of set and setting

Answer 2

Alteration of familiar frameworks:
•	Altered sensory perception & synesthesia (perception of a stimulus in one modality and perceiving it in another) 
•	Altered time and space perceptions
•	Changes in body image and sensations
•	Dissolution of ego boundaries

o Intense mood changes ranging from euphoria to sadness
o Sense of profound meaning or insight; feelings of wonder, awe, beauty, spirituality

Importance of set (mental expectations) and setting (physical environment) = Both influence experience
o Not inherently toxic

Question 3

Describe the major adverse effects of psychedelic drugs

Answer 3

Most common (occurrence < 0.1%) = acute panic reaction (“bad trip”) lasting < 24 hours
• Anxiety, confusion, paranoia
Associated with:
• Drug-taking alone or in an unstructured setting (setting)
• Excessive initial apprehension (set)
• Rigid but brittle psychological defensive structures (set)
• Considerable subsurface guilt and conflict (set)
• Submission to peer pressure as a motive for drug use (set)
• Treatment of choice is reassurance (“talking through”)

Psychosis lasting > 48 hr (occurrence ~ 0.08%)
• History of psychiatric illness or treatment
• History of polydrug abuse

According to a recent report:
• No significant associations between lifetime use of any psychedelics . . .and increased rate of any . . .mental health outcomes. Rather, in several cases psychedelic use was associated with lower rate of mental health problems.

Nausea and vomiting are common with peyote and ayahuasca but are considered beneficial by participants
• Because getting rid of toxins

Question 4

Name four medical conditions under investigation for treatment with psychedelic drugs.

Answer 4

• Advanced cancer = psilocybin
• Treatment of alcoholism and other addictions = Hallucinogens
• Cluster headaches = psilocybin and LSD
• PTSD = MDMA-assisted psychotherapy

Question 5

Explain the role of serotonin receptors in the mechanism of psychedelic drug action.

Answer 5

Increased hallucinogenic potency with increased 5-HT2 receptor affinity

Question 6

Define the term “entactogen” and explain how it came to describe the psychological effects of MDMA; list therapeutic uses for which MDMA is being investigated.

Answer 6

Entactogen = “able to touch within”
o Produce distinctive emotional and social effects

MDMA effects:
o 5-HT, DA, and NE releaser via uptake transporters
o Unique psychological effects
• Feelings of closeness, increased communication, love, mental and physical well-being
• Reduction in fear associated with traumatic events

Possible Therapeutic uses:
o PTSD
o Terminal cancer

Question 7

Describe the receptor pharmacology of cannabinoids.

Answer 7

Main endocannabinoids: 
o	Anandamide (N-arachidonoylethanolamide) 
o	2-arachidonoyl glycerol 
o	Both = Retrograde neurotransmitters = inhibit presynaptic release of NTs like dopamine 

Cannabinoid receptors
CB1
• Inhibits glutamate or GABA release
• Mainly expressed in the brain

CB2
• Abundant in periphery
• Mainly expressed on immune cells (T cells, macrophages, B cells) and hematopoietic cells
• Some expression on peripheral nerve terminals

o Both receptors are coupled to Gi/o → decrease cAMP
o Both CB receptors also activate MAP kinases

Question 8

Describe the physiological and psychological effects of cannabinoids.

Answer 8

o	Euphoria, disinhibition, uncontrollable laughter, changes in perception, achievement of dream-like state
o	Mental concentration = difficult 
o	Vasodilation
o	Increased pulse
o	Chronic users = reddened conjunctiva

Question 9

List four medical conditions for which cannabinoids are efficacious.

Answer 9

• Decrease IOP (glaucoma treatment)
• Antiemetic (good for chemotherapy side effects)
• Appetite stimulant (for AIDS-related anorexia)
• Osteoporosis treatment

Question 10

State how many of the United States currently allow production and use of medical cannabis.

Answer 10

• 20 states and D.C. = medically able to prescribe

* 2 states (Washington & Colorado) = legal