cheat sheet # 2 Flashcards
CNS Analgesics (focus heroin) Endogenous Opioid System
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.
what are dynorhpins ?
Note dynorphins are endogenous peptides but the are the “evil” peptides when released produce dysphoria and unpleasant feelings (more about them later)
What is the greatest concentration of release of these peptides ? (opiod)
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).
Heroin
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.
Characteristics of Heroin (that apply to all opioids)
- 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
Methadone:
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.
Buprenorphine
: 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.
Suboxone:
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.
Naloxone:
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.
Naltrexone:
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.
General effects of CNS depressants
reduced heart rate, breathing, blood pressure, muscle tension/tension
alchohol is a CNS depressants
Effects of Alcohol
- 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)
barbiturates
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.
Benzodiazepine (sedative-hypnotics)
- 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
CNS Stimulants
Cocaine
Cocaine is extracted from coca leaves (used for chewing to help with appetite suppression and working longer hours)
route of administration for cocaine ?
intranasal (snorting), IV and smoking (crack is cocaine freebase)
Effects of cocaine use:
stimulation/energizing, increased heart rate and blood pressure, rush/high (dopamine release in mesolimbic pathway), reduced appetite, heightened senses
High Dose/Chronic Use:
cocaine
: irritability/aggression, insomnia, compulsive motor/limb movement, flight of ideas/incoherent speech, delusions/paranoia
Mechanism of cocaine
blocks monoamine transporter (DA, NE and 5HT – more selective for dopamine)
tolerance of cocaine :
Tolerance: fast tolerance, but seems to plateau (unlike opioids)
Withdrawal: cocaine
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.
Cocaine Incubation:
usually the cravings for the drug decline over time, with cocaine the cravings can get strong with time called the incubation period.
Long-term effects of cocaine:
neurotoxicity (damage to dopamine and serotonin neurons in brain), paranoia/hallucinations, heart failure/death
Amphetamine
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)
Amphetamine and methamphetamine mechanism
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.
Amphetamine (speed
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).
Methamphetamine free based (smoked)
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.
CNS Hallucinogens
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)
Mescaline mechanism:
similar to amphetamine and activates NE
Mushrooms, DMT/Ayahuasca, LSD, Salvia mechanism
binds and releases serotonin (activate 5HT2A amongst other serotonin receptors)
all hallucinogens develops
All hallucinogens develop rapid tolerance (downregulation of 5HT receptors), minimal reward, minimal dependence/withdrawal – less likely to be addictive
Set and Setting determine what ?
the effects people experience(negative or positive) for the hallucinogens: positive mind set and safe environment are critical.
Magic Mushrooms
- 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)
Mescaline/Peyote (cactus)
- Oral administration
- Altered sense of time and awareness, like mushrooms and LSD synesthesia, kaleidoscope of colors
- Can last up to 12 hours
Ayahuasca/DMT (vine)
- 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
LSD (synthetic)
- 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
Salvia (mint plant family)
- 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
bad trip
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.
MDMA
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
MDMA : adverse effects
• Adverse effects: memory problems, paranoia, teeth grinding, sweating, heart racing, panic, vomiting/diarrhea/dehydration
MDMA: reported experience
• Reported experiences: empathy, euphoria, heightened sensations, openness, connection with others, relaxation, sense of inner peace. Altered sense of time
MDMA usually taken ..
• Usually taken orally starts within 30 minutes and can last 3-6 hours
MDMA : charcteristics
- 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
what is ecstasy
Ecstasy is MDMA but includes other substances like caffeine, amphetamine or methamphetamine
CANNABINOIDS
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
ANANDAMIDE
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)
