cheat sheet # 2

Question 1

CNS Analgesics (focus heroin)
Endogenous Opioid System

Answer 1

Central Nervous System has receptors for endogenous opioids (endorphins, enkephalins). Your body releases these peptides in response to pain (physical or psychological pain) to dampen the pain response. Your bodies natural pain killer system. You have opioid receptors that endogenous opioids bind.
Remember endogenous opioids are pain relievers and can produce euphoria/reward sensations (runner high) from natural things like exercise.

Question 2

what are dynorhpins ?

Answer 2

Note dynorphins are endogenous peptides but the are the “evil” peptides when released produce dysphoria and unpleasant feelings (more about them later)

Question 3

What is the greatest concentration of release of these peptides ? (opiod)

Answer 3

There is the greatest concentration of release of these peptides and opioid receptors in the PAG in the midbrain and this is a site where pain signals are modulated going up the spinal cord to the brain and from the brain back to the spinal cord. It has the power to shut down or dampen the pain signal (but does not dampen down the reflexes to withdraw from painful stimuli).

Question 4

Heroin

Answer 4

Heroin is a semi-synthetic extracted from morphine (which is a natural component extracted from opium, a naturally occurring substance). Heroin mimics the endorphins but are more potent and higher concentration because the have a synthetic component.

Question 5

Characteristics of Heroin (that apply to all opioids)

Answer 5

• Rapid tolerance (need a higher dose to get the same effect through repeated use)
• IV heroin use produces severe withdrawal symptoms (fast onset through IV = severe/rapid withdrawal)
• Heroin IV = fast onset (speed) and highly lipid soluble (potent)
• Heroin more potent than morphine (IV heroin v. oral morphine)
• Euphoria is produced: 1) opioid system (like endorphins) are rewarding in and of themselves, 2) opioids inhibit GABA in the mesolimbic pathway (inhibits the inhibitor) = increase dopamine
• Effects of use: pain relief, euphoria, drowsiness/sleepiness, pinpoint pupils, constipation, nausea/vomiting, itching
• Euphoria/rush onset 7-8s and lasts 45s; sedation effects for 1-3 hours; use 2-4 x daily to avoid (every 6-12 hours) withdrawal symptoms
• Effects of high dose: respiratory depression, stop breathing, coma, death
• Withdrawal symptoms (rebound effect): runny nose, restlessness, intense cravings, chills, sweat, anxiety, pain/ irritability, flu like symptoms, restless, dysphoria, insomnia, diarrhea, pupil dilation
• Dangerous – CNS depressant/stop breathing (high dose) – dosing an issue for safety, coma, death, IV dangers, overdose (laced fentanyl), combined cocaine (speedball) effects unpredictable

Question 6

Methadone:

Answer 6

oral administration of an opioid agonist. Because it is oral administration it does not have the same reinforcing effect and the withdrawal symptoms are less severe (but do last longer). This is used to support the heroin detox process to help minimize the severity of withdrawal. The purpose is to slowly tapper the dose down, but for some individual’s methadone is used for maintenance. Methadone is 24-36 hours and only requires being taken 1 time a day. The oral routes and frequency of administration allows more physiological stability, allowing individuals to return to a higher level of functioning.

Question 7

Buprenorphine

Answer 7

: oral administration of an opioid partial agonist. The partial agonist is effective because it binds to the opioid receptors (high affinity) but produces low effects (low efficacy). Because of the low efficacy, there are minimal rewarding effects and the withdrawal symptoms are less severe.

Question 8

Suboxone:

Answer 8

oral administration of buprenorphine and naloxone. When taken orally, only buprenorphine takes effect (see above). When crushed and attempts at injecting (to reintroduce the reinforcing effects of IV opioids), naloxone becomes active and blocks the buprenorphine from taken effect and providing the reinforcing effects. This is used to help with detox or maintenance.

Question 9

Naloxone:

Answer 9

injection in response to opioid overdose. This is a competitive antagonist. It has binding affinity for opioid receptors but produces no effect (no efficacy). It competes with heroin for the opioid receptors and blocks them from producing an effect. It has a shorter half life than heroin, so it has to be administered a few times to offset the overdose. The only problem with competitive antagonists, is that if you take a higher dose of the agonist (heroin) it will override the antagonist.

Question 10

Naltrexone:

Answer 10

used as a form of treatment. The is an antagonist. It is given to only a limited number of individuals who are highly motivated to stop using. As a form of treatment, it does not reduce the cravings that individuals experience, it just blocks the efficacy of future heroin use. Therefore, many individuals discontinue using it because of the strength of the cravings.

Question 11

General effects of CNS depressants

Answer 11

reduced heart rate, breathing, blood pressure, muscle tension/tension

alchohol is a CNS depressants

Question 12

Effects of Alcohol

Answer 12

• Amnesia and memory loss due to blocking of glutamate receptors responsible for forming new memories
• Blackouts and Coma as an agonist at GABA-A receptors (too much GABA)
• Korsakoff Syndrome – nutritional deficiency of vitamin B1 (thiamine). Thiamine is necessary for glucose metabolism, glucose is essential for brain functioning. When there is a disruption with glucose the cells don’t receive nourishment and the die. Treatment would be to administer vitamin B, this stops continued damage, but does not reverse the damage that has already occurred.
• Alcohol is associated with clinical depression (produces dysphoria), but also because of the social isolation and shame aspects
• Chronic alcohol use is associated with problems with the liver, pancreas, blood pressure
• Withdrawal of Alcohol: insomnia, tremors, nausea and seizures, delirium tremors (rebound effect of GABA which triggers release of dopamine and norepinephrine)

Question 13

barbiturates

Answer 13

a cns deppressants
• Reduces anxiety and tension (Ativan, valium, Xanax)
• Binds to GABA – A (does not need the presence of GABA as a gatekeeper) and determines how long the GABA -A channel will be open (more danger if you keep the channels open without a gatekeeper). Because of this function, it isn’t prescribed anymore for anxiety.

Question 14

Benzodiazepine (sedative-hypnotics)

Answer 14

• Reduces anxiety and tension
• Binds to GABA- A (needs the presence of GABA as a gatekeeper to produce an effect) and determines how often the ion channel will be open (less dangerous than keeping the channel open)

a cns depressants

Question 15

CNS Stimulants

Cocaine

Answer 15

Cocaine is extracted from coca leaves (used for chewing to help with appetite suppression and working longer hours)

Question 16

route of administration for cocaine ?

Answer 16

intranasal (snorting), IV and smoking (crack is cocaine freebase)

Question 17

Effects of cocaine use:

Answer 17

stimulation/energizing, increased heart rate and blood pressure, rush/high (dopamine release in mesolimbic pathway), reduced appetite, heightened senses

Question 18

High Dose/Chronic Use:

cocaine

Answer 18

: irritability/aggression, insomnia, compulsive motor/limb movement, flight of ideas/incoherent speech, delusions/paranoia

Question 19

Mechanism of cocaine

Answer 19

blocks monoamine transporter (DA, NE and 5HT – more selective for dopamine)

Question 20

tolerance of cocaine :

Answer 20

Tolerance: fast tolerance, but seems to plateau (unlike opioids)

Question 21

Withdrawal: cocaine

Answer 21

only 5-6% after initial use of cocaine go onto dependence. Cocaine not typically associated with development of dependence. Reasons could be the initial crash/come-down after single use stops people from using again (crash dysphoria, anxiety, insomnia) and cost associated with cocaine/availability/legal consequences. Reasons people do develop dependence: 1) binge cycles in response to attempts to stop the “crash”, 2) taking higher doses, 3) transition from intranasal to IV or smoking.

Question 22

Cocaine Incubation:

Answer 22

usually the cravings for the drug decline over time, with cocaine the cravings can get strong with time called the incubation period.

Question 23

Long-term effects of cocaine:

Answer 23

neurotoxicity (damage to dopamine and serotonin neurons in brain), paranoia/hallucinations, heart failure/death

Question 24

Amphetamine

Answer 24

Amphetamine is a fully synthetic stimulant that mimics naturally occurring ephedrine (used as a diet pill and wakefulness pill)
Derivatives of amphetamine are methamphetamine and MDMA - usually taken orally (but IV and snorting is always available with pills that can be crushed)

Question 25

Amphetamine and methamphetamine mechanism

Answer 25

cause the transporters to scoops monoamines into the axon terminal forcing the release of vesicles into the cytoplasm in the axon terminal and then scoops them back into the cleft – producing more in the cleft. The are also known for inhibiting the enzyme MAO which is known for breaking down the monoamines.

Question 26

Amphetamine (speed

Answer 26

Ritalin and Adderall are treatment for ADHD (hypothesis of cause of ADHD is under activation in prefrontal cortex, Ritalin brings them back to “baseline”) which are prescriptions available in pill form. These are often covered under insurance and are less expensive. There is an “epidemic” in the US of youth taking non-prescribed Ritalin and Adderall to enhance concentration. Unlike cocaine, amphetamine use is associated with improvement in attention and memory (also can work longer hours and need less sleep).

Question 27

Methamphetamine free based (smoked)

Answer 27

is more potent than amphetamine and can be less expensive/significantly. The route of administration and potency of crytal meth increase the rates of abuse and dependence.

Question 28

CNS Hallucinogens

Answer 28

This class of drugs is known for altered states of consciousness and altered perceptual experiences, which is why it has been known in the past as psychedelic (altered consciousness), psychotomimetic/ psychotogenic (produces psychosis/altered perceptual experiences) 
There is a serotonin receptor in the brain known as 5HT2A and this receptor is associated with producing hallucinations (it has now become a target for treatment in schizophrenia)

Question 29

Mescaline mechanism:

Answer 29

similar to amphetamine and activates NE

Question 30

Mushrooms, DMT/Ayahuasca, LSD, Salvia mechanism

Answer 30

binds and releases serotonin (activate 5HT2A amongst other serotonin receptors)

Question 31

all hallucinogens develops

Answer 31

All hallucinogens develop rapid tolerance (downregulation of 5HT receptors), minimal reward, minimal dependence/withdrawal – less likely to be addictive

Question 32

Set and Setting determine what ?

Answer 32

the effects people experience(negative or positive) for the hallucinogens: positive mind set and safe environment are critical.

Question 33

Magic Mushrooms

Answer 33

• Eat/Food + Drink/Tea (naturally occurring mushroom)
• Psilocybin turns into psilocin in the brain with a 30 min onset and lasts about 6 hours
• Epiphanies, clarity, hallucinations, vibrant colors, happiness, synesthesia (eg. Color experienced as a sound – cross wiring of your perceptual senses)

Question 34

Mescaline/Peyote (cactus)

Answer 34

• Oral administration
• Altered sense of time and awareness, like mushrooms and LSD synesthesia, kaleidoscope of colors
• Can last up to 12 hours

Question 35

Ayahuasca/DMT (vine)

Answer 35

• DMT is a naturally occurring substance in the brain (believed to be released from the pineal gland – see Dr. Rick Sassman, the pineal gland was once identified by Descartes as the seat of the soul). Many believe endogenous DMT might account for the spiritual experiences people have during activities like meditation.
• DMT is 2 steps removed from tryptophan (tryptamine molecule is an analog of serotonin). DMT is broken down in the stomach by the enzyme MAO – therefore, when taken orally there must be a substance included that inhibits MAO enzymes to allow the effect.
• Reported experiences: mystical/transcendental experiences, disintegration of the ego/body with only a spirit remaining, profound connection of one’s spirit with the universe, loss of sense of body, soul and spirit are one with universe, only the present exists. Usually only lasts 1 hour – 3 hours

Question 36

LSD (synthetic)

Answer 36

• Effects: synesthesia, open/closed eye visual hallucinations, dissociation/depersonalization, distorted sense of time. Can produce a “bad trip” filled with anxiety and paranoia.
• Usually lasts up to 8 hours

Question 37

Salvia (mint plant family)

Answer 37

• Very short acting starts within seconds and lasts up to an 1 hour
• Reported Experiences: Can be a dark experience with uncontrollable laughter, visiting the past, becoming an object, out of body experiences, connecting with other dimensions, loss of contact with reality

Question 38

bad trip

Answer 38

anxiety, paranoia, sense of going insane, extreme disorientation, wanting to harm oneself — it is hard to identify when someone will have a bad trip from a hallucinogen, but many people believe that set and setting contribute to this phenomenon.

Question 39

MDMA

Answer 39

MDMA is a synthetic derivative of amphetamine (stimulant) – high release of serotonin – it acts like a hallucinogen because of the flush of serotonin, but also acts like a stimulant because it is a derivative of amphetamine
Fast tolerance develops, associated with fast depletion of serotonin (rebound after can be mood disturbances), minimal physical dependence or withdrawal

Question 40

MDMA : adverse effects

Answer 40

• Adverse effects: memory problems, paranoia, teeth grinding, sweating, heart racing, panic, vomiting/diarrhea/dehydration

Question 41

MDMA: reported experience

Answer 41

• Reported experiences: empathy, euphoria, heightened sensations, openness, connection with others, relaxation, sense of inner peace. Altered sense of time

Question 42

MDMA usually taken ..

Answer 42

• Usually taken orally starts within 30 minutes and can last 3-6 hours

Question 43

MDMA : charcteristics

Answer 43

• Used in the past for psychotherapy to open people to the experience
• Animal studies have shown the MDMA produces neurotoxic effects on serotonin neurons, but this hasn’t been replicated in humans (there is a large debate on this issue)
• FDA approved for research and is being considered an important component to explore in the treatment of PTSD (if trials work it might be legal by 2021) – helps with processing experience and feeling empathic towards oneself
• MDMA flashbacks – usually within 3 weeks of using, triggered by stimuli used at the time/stimuli associated with using

Question 44

what is ecstasy

Answer 44

Ecstasy is MDMA but includes other substances like caffeine, amphetamine or methamphetamine

Question 45

CANNABINOIDS

Answer 45

Naturally occurring cannabis plant/hemp plant – contains 70 unique cannabinoids (eg. THC, cannabinol, CBD)
THC is the main psychoactive component associated with the “high” /euphoria/relaxation

Question 46

ANANDAMIDE

Answer 46

is a lipid that is naturally occurring in the brain (cannabis mimics anandamide) that binds to CB receptors. Anandamide is a retrograde messenger, meaning it is released from the postsynaptic site and binds to CB1 receptors located on the axon terminal. CB1 receptors are responsible for inhibiting calcium entrance (calcium is needed for the vesicles to fuse and release from the axon terminal). Therefore, substances that bind to CB1 play a role in the inhibition of the release of neurotransmitters from the axon (monoamines, GABA, glutamate). Anandamide plays a role in pain, motivation, sleep, eating and reward. Cannabinoids bind to CB1 receptor and mimics effects of anandamide – why it is relevant for treatment of pain and loss of appetite (cancer patients)