Med-Neuro: Marijuana and Hallucinogens

Two Notable Endocannabinoids

1. Anandamide (AEA) 2. Arachidonoylglycerol (2-AG)

What are the four stages of marijuana use?

1. Buzz: feel lightheaded or even slightly dizzy 2. High: feeling of euphoria and exhilaration as well as sense of disinhibition 3. Stoned: feels calm, relaxed, and perhaps even in a dreamlike state 4. Come-Down: gradual cessation of these effects

What are the two receptors that respond to cannabinoid binding?

1. CB1 2. CB2

Two Synthetic Full Agonists for CB1 and CB2

1. CP-55, 940 2. WIN 55, 212-2

What are two results of heavy cannabis use in adolescence?

1. Cognitive Deficits 2. Amotivational Syndrome

What are three adverse effects of cannabis intoxication?

1. Decreased Memory 2. Decreased Psychomotor Performance 3. Other Cognitive Functions

What are the five feelings induced by cannabis intoxication?

1. Euphoria 2. Disinhibition 3. Relaxation 4. Altered Sensations 5. Increased Appetite

What are the two enzymes that break down endocannabinoids?

1. Fatty Acid Amide Hydrolase (FAAH) 2. Monoacylglycerol Lipase (MAGL)

Two Chemical Classifications of Hallucinogens

1. Indoleamines 2. Phenethylamines

What are the four phases of an LSD trip?

1. Onset 2. Plateau 3. Peak 4. "Come Down"

What are four roles of the endocannabinoid system?

1. Pain Sensitivity 2. Hunger and Eating Behavior 3. Learning and Memory 4. Extinction of Fear Responses

What are three health consequences of marijuana?

1. Respiratory Problems 2. Possible Immunosuppression 3. Interference with the Reproductive System

What are four acute effects of dissociative anesthetics, such as phencyclidine and ketamine?

1. Sensory Distortions 2. Altered Body Image 3. Cognitive Disorganization 4. Affective Changes

An ER patient presents with an OD. All that you know is that he OD'd on some street drug. What should be done in an attempt to determine the drug taken by this patient?

A blood or urinalysis should be done in an attempt to determine the drug taken by this patient; however, these labs may not always detect the compound.

What is a possible use of hallucinogenic drugs, such as psilocybin?

A potential use of hallucinogenic drugs, such as psilocybin, is for the treatment of drug addiction and depression. This is because these drugs have dramatic effects in essentially shutting down brain circuits, resetting the system.

Phencyclidine (PCP) Street Name

Angel Dust

Which of the following is a therapeutic indication for dronabinol? A. Depression B. Appetite Stimulation C. Glaucoma D. Migraine

B. Appetite Stimulation

A 13-year-old child is brought in by his mother because he is acting strangely. He has become "lazier" at school, and, as a result, his grades have decreased. She believes that he has been more depressed because he spends his free time sitting in his room and eating more than usual. On physical exam, you notice injected conjunctiva, but no other pertinent findings. What is the best next step? A. Referral to a psychiatrist for depression B. Urine drug screen C. Call child protective services D. Referral to ophthalmologist

B. Urine drug screen

What is the role of dissociative anesthetics, such as phencyclidine and ketamine, in drug addiction?

Both PCP and ketamine are reinforcing to animals, as indicated by drug self-administration. NMDA receptors play a role in the development of drug addiction, so these reinforcing effects may be mediated by both dopaminergic and non-dopaminergic mechanisms.

Which of the following illicit drugs is most commonly abused by adolescents? A. Anabolic Steroids B. Crack Cocaine C. Marijuana D. Heroin

C. Marijuana

2-AG binds to ___.

CB1

What happens when the CB1 receptor is activated?

CB1 activation induces reduced locomotor activity, hypothermia, catalepsy, and hypoalgesia.

Anandamide binds to ___.

CB1 and CB2

What happens when the CB2 receptor is activated?

CB2 activation causes cytokine release and changes in immune cell migration toward an inflammatory site.

What is the effect of cannabinoid intoxication on dopamine signaling?

Cannabinoid reinforcement has been shown to depend on the CB1 receptor and involve dopamine since cannabinoids stimulate the firing of DA neurons in the VTA and enhance DA release in the nucleus accumbens.

What is the active constituent of marijuana? A. Methamphetamine B. Lysergic Acid Diethylamide C. Heroin D. Tetrahydrocannabinol

D. Tetrahydrocannabinol

What is dronabinol? What is it used for?

Dronabinol is a synthetic THC used for treating nausea and vomiting in cancer chemotherapy patients as well as stimulating appetite in AIDS patients.

Drug or Compound: 3,4-Methylenedioxy-Methamphetamine Common Name: Details:

Drug or Compound: 3,4-Methylenedioxy-Methamphetamine Common Name: MDMA or "Ecstasy," "Adam," and "Love Drug" Details: MDMA is a sympathomimetic that causes hyperthermia, seizures, cerebral hemorrhage, hyponatremia, and arrhythmias. It is associated with interpersonal closeness, emotional awareness, euphoria.

Drug or Compound: Lysergic Acid Diethylamide Common Name: Details:

Drug or Compound: Lysergic Acid Diethylamide Common Name: LSD or "acid" Details: LSD is a potent hallucinogen that comes in tablet and paper forms.

Drug or Compound: N,N-Dimethyltryptamine Common Name: Details:

Drug or Compound: N,N-Dimethyltryptamine Common Name: DMT or "businessman's trip" Details: DMT is a hallucinogenic found in South American plants and ayahuasca brews. It is prepared as snuff from leaves, seeds, and pods and has a short duration of only a minute.

How are cannabinoids extracted from marijuana?

Either marijuana, the leaves, or hashish, the resin, are ground into a powder. The pure compounds, the cannabinoids, are isolated away from the non-pure compounds, or the non-cannabinoids.

What type of messenger are endocannabinoids? How do they work?

Endocannabinoids, including 2-AG and AEA, function as retrograde messengers since they are synthesized and released from postsynaptic cells and act on nearby nerve terminals to inhibit neurotransmitter release by inhibiting the opening of voltage-gated Ca+channels on the presynaptic cell. It decreases presynaptic GABA release and allows the the postsynaptic cell to fire more.

True or False: Every state that has legalized the medicinal use of marijuana uses marijuana for the same illnesses.

False

True or False: Individuals can form dependence to hallucinogens.

False

True or False: Phencyclidine has significant applications in both human and veterinary medicine.

False: Ketamine

Cannabinoid receptors are ___________ receptors.

G-protein coupled (Gi/o)

What is the order in which THC affects bodily tissues?

If an individual smokes marijuana, the first bodily system affected is the blood. Within 30 minutes, the peak concentration of THC in the blood plasma has reached its peak. Next, the brain is affected, and the effects of THC on the brain can last for a day. Then, THC is absorbed by highly perfused tissues, low perfused tissues, and then is transformed to be stored in fat.

Synthetic Cannabinoid Street Names

K2, Spice, Mr. Nice Guy, Genie

What is the mechanism of action of ketamine?

Ketamine binds to a site within the NMDA receptor channel, thereby acting as noncompetitive receptor antagonist. A secondary consequence of this NMDA receptor blockade is increased presynaptic glutamate release, which may contribute to the behavioral and subjective effects of ketamine.

What are the subjective effects of LSD?

LSD, like other hallucinogens, are known for triggering trips. During the trip, the user experiences vivid visual hallucinations, a slowing of the subjective sense of time, feelings of depersonalization, strong emotional reactions, and a disruption of logical thought. However, the use of LSD can also lead to adverse effects such as "bad trips" and flashbacks.

What is medical marijuana? Does it actually work?

Medical marijuana refers to the use of smoked marijuana as a medication. It is supported by anecdotal reports from the patients that smoking cannabis gives them greater symptom relief than oral medications.

What is the onset of most hallucinogenic drugs? What are the two exceptions?

Most hallucinogenic drugs are orally active with a slow onset of action and a long course of action. The two exceptions are DMT and Salvia, which are usually smoked, thereby leading to rapid drug effects and a much shorter duration of action.

What is nabilone? What is it used for?

Nabilone is a THC analog used in treating nausea and vomiting in cancer chemotherapy patients as well as stimulating appetite in AIDS patients.

What is nabiximols? What are they used for?

Nabiximol is a cannabis extract containing THC and cannabidiol that is taken as an oral spray for the treatment of neuropathic pain and spasticity in multiple sclerosis patients.

What is the most potent hallucinogen? Least potent?

Of commonly used hallucinogens, LSD is the most potent while mescaline is the least potent.

What route of administration of THC has been shown to reduce withdrawal symptoms in heavy marijuana use?

Oral THC has been shown to reduce withdrawal symptoms in heavy marijuana use.

Why are PCP and ketamine known as dissociative anesthetics?

PCP and ketamine are known as dissociative anesthetics because they induce hallucinations.

What is the mechanism of action of phencyclidine?

PCP binds to a site within the NMDA receptor channel, thereby acting as noncompetitive receptor antagonist. A secondary consequence of this NMDA receptor blockade is increased presynaptic glutamate release, which may contribute to the behavioral and subjective effects of PCP.

What is the main target of serotonergic hallucinogens?

Recent research has implicated combined 5-HT2A and glutamate activation of pyramidal neurons in the prefrontal cortex, at least in the case of the indoleamine and phenethylamine hallucinogens, are the main targets of these hallucinogens.

What is perhaps a novel therapeutic use of ketamine?

Several studies suggest that ketamine may have novel therapeutic applications in the treatment of major depression and for pain relief. Since SSRIs take nearly 6-8 weeks to experience the full effect, it is important for patients to experience relief from depression prior to this time period. Ketamine, a fast-acting antidepressant, can be used for the first two weeks of treatment in order to rapidly increase synapse number and function as well as reverse the synaptic deficits caused by chronic stress by regulating glutamatergic signaling.

Ketamine Street Name

Special K

What are synthetic cannabinoids?

Synthetic cannabinoids are compounds that were originally used as research compounds to determine affinities at CB receptors. However, now these compounds are used in e-cigarettes as well as in an aerosol form, which is sprayed on non-discriminate leaves and smoked.

Why are synthetic cannabinoids dangerous?

Synthetic cannabinoids are dangerous because they are very difficult to purify, so they contain impurities.

How is THC metabolized?

THC is extensively metabolized in the liver, and the metabolites are excreted mainly in the feces and urine. Total clearance of the drug and its metabolites may take days to weeks because of sequestration of these compounds in fat tissue.

What is the principle cannabinoid receptor of the brain? Where is it expressed?

The CB1 receptor is the principal cannabinoid receptor in the brain, where it is expressed at a high density in the basal ganglia, cerebellum, hippocampus, and cerebral cortex presynapse. These parts of the brain are involved in movement and cognition.

Where is CB2 found?

The CB2 receptor was first identified in the immune system, but it is also found in a number of other tissues including the brain, where it is mainly localized in microglial cells.

Why are there receptors for cannabinoids in the body?

The brain synthesizes several substances, called endocannabinoids, which are neurotransmitter-like agonists at cannabinoid receptors. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are examples of these endocannabinoids. Anandamide and 2-AG are degraded primarily by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL).

What is the core compound of marijuana?

The core compound of marijuana is tetrahydrocannabinol (THC), which is a psychostimulant.

Is marijuana safe to use?

Yes and no. When compared to even drugs like nicotine, marijuana does not result in hard withdrawal symptoms. However, marijuana is known as a gateway drug, although the results are not conclusive.

Does marijuana use result in withdrawal?

Yes, heavy marijuana users are at significant risk for developing dependence on the drug and for undergoing withdrawal symptoms.

What is the effect of marijuana on the amygdala?

The effect of marijuana on the amygdala is increased anxiety and paranoia.

What is the effect of marijuana on the cerebellum?

The effect of marijuana on the cerebellum is decreased motor control.

What is the effect of marijuana on the hippocampus?

The effect of marijuana on the hippocampus is impaired learning.

What is the effect of marijuana on the hypothalamus?

The effect of marijuana on the hypothalamus is to induce hunger.

What is the effect of marijuana on the neocortex?

The effect of marijuana on the neocortex is altered senses and disordered thinking.

What is the effect of marijuana on the ventral striatum?

The effect of marijuana on the ventral striatum is euphoria and relaxation.

What is the most common subjective effect of marijuana use?

The feeling of being stoned, where a user feeling calm, relaxed, or even in a dreamlike state, is the most common effect.

What is the most important naturally-occurring cannabinoid?

The most important naturally occurring cannabinoid is Δ9-tetrahydrocannabinol (THC).

Amotivational Syndrome

a pattern of behavior connected to cannabis use characterized by apathy and loss of achievement motivation

Hallucinogen

a substance that causes perceptual and cognitive distortions in the absence of delirium

What is cannabinoid tolerance related to?

Tolerance is related to a desensitization and down-regulation of central CB1 receptors.

True or False: Around 60% of the US population lives in a state where marijuana has been legalized.

True

True or False: Early behavioral problems have been associated with an increased likelihood of early marijuana use.

True

True or False: Hashish has a higher potency than cannabis itself.

True

True or False: Phencyclidine was withdrawn from clinical use because of its prominent adverse side effects.

True

Endocannabinoid

an endogenous neurotransmitter-like agonist at cannabinoid receptors

Street Drug

an illegal drug of usually an unknown mixture of ingredients to dilute or enhance the drug

If sedation and traquiliation is indicated in a patient that has overdosed on hallucinogens, the patient should be treated with ____________.

benzodiazepines and/or antipsychotics

Ketamine Drug Class

dissociative anesthetic

Phencyclidine (PCP) Drug Class

dissociative anesthetics