Term
| What type of drug is cannabis? |
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Definition
- very hard to classify
- has sedative, psychedelic, and analgesic effects
- many describe it as a depressant, but it is also both classified as a narcotic and psychedelic drug
- its unique effects and pharmacology justify cannabis a separate classification
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Term
| Cannabis's Uses and History |
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Definition
- Uses
- hemp - parts of plant excluding buds and leaves that are low in thc and can be used for structural purposes
- buds and leaves can be dried and used for psychoactive and medicinal effects
- thc found in resin of plant
- history
- cannabis usage can be traced back 8000B.C.E. (particularly for its use in fabrics)
- notable uses in china as medicine, religion in india, and problems w/ abuse as hashish in arab world around 1000 AD
- marijuana legislation in new world can be seen in 1619 through Jamestown colony
- at turn of 19th century it became in vogue as a popular drug among artists and writers
- by 1930's interest of general public aroused through increased publicity
- particularly negative interest
- Reefer Madness
- increased recreational interest resulted as well as increased regulation
- Henry Anslinger spearheaded anti-pot movement determining it to cause permanent brain damage and incite violent behavior with no scientific backing
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Term
| Different Cannabis Preparations and Potency |
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Definition
- Hashish = 7-14% THC
- Hash Oil = 15-60% THC
- Marijuana = 2-5%
- high potency pot began coming from Mexico and Colombia in the 60s and 70s
- US backlash led to cleaner pot w/ less pesticides (periquot) with the development of home growing and experimentation
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Term
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Definition
- Marijuana Tax Act - 1937
- possession of marijuana w/out having paid special tax considered a federal crime
- enforcement resulted in arrests for simply paying tax
- ruled unconstitutional in 1960
- Comprehensive Drug Abuse Prevention and Control Act
- made marijuana a schedule I drug
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Term
| Smoking vs. Edible Consumption of Cannabis |
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Definition
- Marijuana is usually smoked
- THC is rapidly absorbed through the lungs
- Most of the THC is gone in a few hours, but it can accumulate in organs in the body (depot-binding)
- Half-life for THC is ~20-30 hours
- With a large dose of THC, metabolites of it can be in the body for up to 3 weeks
- THC is very lipid-soluble
- Edibles
- Less THC gets to the brain (due to first-pass metabolism)
- Takes longer for the THC to get to the brain
- The effects of the THC take longer to start and generally last longer
- However, the high can be more intense than with smoking because it is easy to take more THC than with smoking
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Term
| Cannabinoid Pharmacodynamics |
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Definition
- work through endogenous cannabinoid receptors
- usually activated by endocannabinoids
- receptors can be found in brain, immune system, and GI tract
- may play a role in learning, controlling anxiety and reducing perception of pain
- decrease neurotransmitter release
- inhibit acetylcholine in hippocampus (bad memory)
- inhibit norepinephrine release
- also inhibit glutamate and GABA release
- PNS: sympathetic nerve terminals
- CNS: hippocampus, cerebellum, cerebral cortex, amygdala, basal ganglia
- come in two varieties: CB1 and CB2
- both are metabotropic
- CB1 receptor
- mostly localized in CNS and mediate psychoactive properties
- found on many locations of neuron including axon, cell bodies, and dendrites
- CB2 receptor
- most localized in periphery and mediate effects on immune system
- likely also cause aversive effects associated w/ THC
- receptors typically found on the presynaptic neurons
- endocannabinoids released from postsynaptic neurons alter transmitter release from presynaptic neuron
- mechanism of action involves actions of βγ subunits
- inhibition of adenylyl cyclase and cAMP system (Protein kinase A inhibits K+ channels less allowing current efflux)
- direct enhancement of inward-rectifying K+ channels
- inhibition of calcium channels
- α subunit
- enhance MAP kinase -> ?
- inhibit sodium channels
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Term
| Actions of Cannabinoid Receptors in Brain |
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Definition
- general effects of cannabinoids on brain are similar to those of opiates and alcohol in that they decrease overall activity
- Cerebral Cortex (especially the frontal cortex):
- dreamlike state of the high
- distortion in time, sound, color, taste, ability to concentrate, and mood effects
- Basal Ganglia and Cerebellum:
- effects on movement and postural control (not unlike alcohol)
- Hippocampus:
- disruption of memory and memory storage
- Hypothalamus:
- decreased production of reproductive hormones
- One rumor is that it would make you sterile = not true
- However, it can make it more difficult to reproduce (get pregnant or get somebody pregnant)
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Term
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Definition
- Anandamide - first discovered
- very lipid soluble
- has marijuana-like effect when administered to animals
- the normal role of endocannabinoids is not entirely understood
- they do modulate acetylcholine transmission and likely have purpose in memory, but specific role in memory consolidation not understood
- 2-AG - far more common than anandamide
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Term
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Definition
- appetite stimulation commonly found in American culture is actually subject to placebo effect
- sometimes used as appetite suppressant in Jamaican culture
- heart
- increased rate
- risk for those w/ heart problems
- lungs
- reduced airflow
- almost definite risk for lung cancer when smoked
- because it does not affect breathing center or other brainstem structures, it is much safer than drugs like alcohol, barbiturates, or opiates
- reproductive system
- won't make people sterile but will make it more difficult to reproduce due to effects on hormones
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Term
| Psychological Effects of THC and Subjective High |
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Definition
- To a certain extent, one has to learn
- technique (how to smoke marijuana)
- what to expect behaviorally
- how to titrate the dose
- Most users do not get high the first time they use marijuana
- Also explains the big placebo effect with marijuana
- Typical effects include initial anxiety or tension gradually replaced by feelings of well being. Eventually the user becomes introspective and tranquil.
- May see rapid mood changes - hilarity followed by contemplative silence
- User is bombarded by loosely associated thoughts.
- Often lead to the belief that one has gained great insights, but ability to analyze them is impaired. After intoxication, these great insights often turn out to be mundane ideas.
- Increased awareness of surroundings - enhanced sensory perception and imagery
- Euphoria - not always observed, and may be intermingled with mild anxiety, paranoia, or fear - A fear that one has lost control of the experience and things will never return to normal
- Sedation - variable
- Everything seems funny
- Enhanced feelings of creativity
- Decreased motor skills
- Sensation of time slowing down
- high is extremely variable and can include some of the following symptoms:
- Increased sensory perception
- Visual images may seem more intense or more meaningful
- Feelings often seem more intense
- Many users find it hard to describe the high
- cognition changes typically viewed as positive, but depend on the situation one is in
- hallucination, paranoia, and agitation can occur at higher doses
- another hallmark characteristic is an impairment to creating new memories w/out affecting recollection of old ones
- thc actually decreases memory in a dose-dependent manner
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Term
| THC Tolerance and Independence |
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Definition
- tolerance
- tolerance can develop but it is not as definitive as w/ other drugs
- pharmacodynamic tolerance, particularly down-regulation of cannabinoid receptors, has been evidenced
- dependence
- ~10% of people who try marijuana become dependent
- instances of significant cravings rare
- inability to control use of the drug in manner similar to amphetamines or other more addictive drugs also rare
- however, reports of compulsive and unstoppable use are becoming increasingly common
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Term
| Addiction and Withdrawal from THC |
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Definition
- due to a lack of evidence of marijuana's effect on the reward pathway, it was originally thought to not be addictive
- more recent studies have shown an increase in dopamine release from the VTA to NAc
- dopamine levels increase over saline in presence of THC
- effect negated by CB1 receptor antagonist and opioid receptor antagonist naloxone
- suggestive of opioid receptor being part of response
- It is possible that it may not activate this connection to the extent that amphetamines or other addictive drugs do, but it may increase dopamine release in a manner similar to food or sex
- withdrawal is usually mild and includes symptoms like irritability, restlessness, insomnia, sweating, mild nausea, depressed mood - akin to withdrawal from nicotine
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Term
| Will Animals Self-Administer THC? |
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Definition
- animals will self administer
- as gold standard, this demonstrates the reinforcing properties of the drug
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Term
| Potential Mechanism for THC-induced increase of Dopamine in NAc |
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Definition
- THC decreases GABA inhibition of VTA allowing increased release of dopamine onto NAc
- opioid receptors are also likely associated w/ this mechanism in some way
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Term
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Definition
- Δ9-THC, the main psychoactive compound of cannabis, is highly lipid soluble and has a half-life of ~2.5 days
- Carboxy-THC is the main metabolite of Δ9-THC
- not psychoactive
- lipid-soluble
- half-life of 5-6 days
- main metabolite tested for in blood and urine tests
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Term
| Does Marijuana Use Cause Permanent Damage? |
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Definition
- Does it kill brain cells?
- It is still not clear which changes in brain function are permanent and which are not
- This is very difficult to study, in part because you can’t control the amount of marijuana people take very well over time
- Currently, most of the scientific evidence suggests that for most doses and rates of use, most people do not experience loss of neurons from using marijuana
- That said, there might be subtle types of damage caused by recreational marijuana use that haven’t been identified
- permanent damage from use during adolescence
- if cannabis use changes the way that neurons connect this will cause permanent changes in less flexible adult brain
- cognitive impairments
- These may be long-lasting, and this may be particularly true of people who start in their teens
- But studies of occasional recreational use are difficult to do
- psychological impairments
- Marijuana use can cause psychotic symptoms (hallucinations, delusions) similar to those experienced in schizophrenia
- The vast majority of users never show these symptoms, but what if someone is predisposed to psychosis (such as for genetic reasons)?
- There is clear evidence that smoking pot during adolescence increases a person’s risk of developing schizophrenia. (especially in males)
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Term
| Gateway Hypothesis of Marijuana Use |
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Definition
- Means that chronic marijuana smoking will lead to the use of other more harmful drugs
- People who are interested in expanding their consciousness and experiencing drugs will do it
- Another reason people will try other drugs if they smoke marijuana results from the people they associate with
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Term
| Marijuana and Amotivational Syndrome |
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Definition
- Means that chronic marijuana smoking is responsible for a generalized sense of apathy and indifference to long term plans and goals
- Marijuana may be one factor out of many that determines a persons choices in life
- Human studies have not shown significant evidence to support this
- the symptoms of this may be better regarded as the symptoms of chronic cannabis intoxication
- animal research has found otherwise as monkeys have been shown to have decreased motivation
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Term
| Potential Long-term Toxicities of THC |
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Definition
- impairment of motor skills
- panic reactions
- pulmonary disease - basically same as cigarette smoking
- reproduction
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Term
| Medical Uses for Marijuana |
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Definition
- control of nausea/vomiting from chemotherapy
- A drug called “Marinol”, is actually used for this and classified as a DEA schedule II drug, but some say it is not as effective as marijuana itself.
- Also “Cesamet” – is a synthetic analog of THC approved for medical use.
- Both drugs are taken orally
- anorexia and appetite loss
- cachexia/wasting syndrome associated w/ HIV/AIDS and cancer
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Term
| Serotonin-related Psychedelics |
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Definition
- also known as indole hallucinogens
- serotonin is an indolamine
- related to dopamine, epinephrine, and norepinephrine
- also chemically distinct in that it uses its own set of enzymes for production
- important in regulating mood, level of general arousal, depression, smooth muscle contraction, blood vessel constriction
- Main examples:
- Lysergic Acid Diethylamide (LSD)
- Psilocybin
- Lysergic Acid Amide
- Dimethyltryptamine (DMT)
- Bufotenine
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Term
| Acetylcholine-related Psychedelics |
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Definition
- Atropine
- Scopolamine
- Ibotenic Acid
- Ibogaine
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Term
| Glutamate-related Psychedelics |
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Definition
- PCP - phencyclidine
- Ketamine
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Term
| Catecholamine-related Psychedelics |
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Definition
- Mescaline
- DOM (STP)
- MDMA (ecstasy)
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Term
| Reinforcement and Psychedelics |
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Definition
- Most gain their reinforcing value for humans because of their ability to alter consciousness and perceptual processes, rather than because they exert their effects on the primary rewards centers of the brain
- animals will not self-administer
- administer for experience - not the mood/emotions
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Term
| LSD/Lysergic Acid Diethylamide |
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Definition
- synthesized from ergot alkaloids extracted from ergot fungus that grows on rye and other grains
- Albert Hoffman synthesized it for Sandoz pharmaceutical company 1938
- first to describe effects after accidentally ingesting
- took a second dose later on of 250ug
- remarkable potency - detectable effects @ 50ug
- 250ug is a high dose of LSD whereas this amount of most other drugs would produce no effect
- alcohol literally requires grams to elicit a desired reaction
- extremely high potency allows users to take minute amounts making it very difficult to detect in body
- early uses aimed @ using drug to reveal biochemical basis of psychosis, while later uses went towards use in psychotherapy and eventually as an abusable drug
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Term
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Definition
- high lipid solubility
- absorbed 30 to 60 minutes after ingestion
- easily crosses BBB
- half-life of 3 hours and stays in body up to 12 or 15 hours
- extremely high potency makes for difficult detection
- binding sites located throughout brain - RAS of particular interest
- metabolized by liver and excreted through liver
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Term
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Definition
- initially excites sympathetic activity
- increased heart rate
- increased blood pressure
- dilation of pupils
- increase in body temperature
- only 1 reported case of LSD being fatal
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Term
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Definition
- Very subjective and depend on context
- Religious feelings followed by sexual feelings followed by sadness, anxiety, and paranoia
- Breaks with reality
- Develop insights
- Perceptual alterations- out of body experience
- Higher doses, actual hallucinations
- Synesthesia – smell colors/see sounds
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Term
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Definition
- many myths exist but most likely explanation is that these are memories or a condition somewhat related to PTSD
- some false myths
- LSD sequestered in adipose tissue and slowly released as it is burned
- slow, random release from CSF
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Term
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Definition
- LSD resembles serotonin - effects serotonin receptors
- it appears that some of the hallucinogenic effects occur due to LSD being a potent agonist of 5-HT2 receptors (postsynaptic)
- activity influenced in forebrain and midbrain
- activity also altered in RAS, causing arousal and alertness
- RAS no longer filters sensory information - leads to a flood of information reaching the conscious - probably how LSD "expands" the mind
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Term
| Tolerance and Dependence w/ LSD |
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Definition
- not likely to result in drug dependence for 3 reasons
- hallucinogens (cross-tolerant) build up tolerance faster than any other class of drug
- not an easy high (not typical ‘fun’)
- experience controls the user - can't come down at will (unpredictable effects)
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Term
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Definition
- found in various North American mushrooms
- considered sacred in by native peoples in Mexico and Central America for thousands of years
- Albert Hoffman also isolated psilocybin from mushrooms
- isolated from mushrooms
- ~15 species that vary widely in psilocybin and psilocin content
- dried mushrooms contain on average 0.4% psilocybin
- ROA
- once ingested, it becomes psilocin - this is what acts in brain
- potency 100x less than acid - 4-8mg
- effects appear w/in 30 minutes of ingestion and last 2-4hrs
- serious danger is accidentally eating toxic mushrooms that look like psychedelic ones
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Term
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Definition
- effects similar to LSD but milder
- pleasant mellow feeling with mental relaxation similar to cannabis
- increased heart rate and blood pressure
- increased body temperature
- pupillary dilation
- at higher doses ‑ hallucinations, time and space distortions.
- higher doses can cause stomach pain, nausea and vomiting, shivering, loss of coordination
- extremely high doses can cause convulsions - psilocybin unlike acid is actually somewhat toxic
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Term
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Definition
- Psilocybin's mechanism mirrors that of LSD
- it appears that some of the hallucinogenic effects occur due to psilocybin being a potent agonist of 5-HT2 receptors (postsynaptic)
- activity influenced in forebrain and midbrain
- activity also altered in RAS, causing arousal and alertness
- RAS no longer filters sensory information - leads to a flood of information reaching the conscious
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Term
| Tolerance and Withdrawal of Psilocybin |
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Definition
- tolerance develops to psilocin and cross tolerance exists between LSD and psilocin
- withdrawal symptoms are mild ‑ headache and fatigue
- minimal potential for physical or psychological dependence
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Term
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Definition
- close relative to LSD
- another drug discovered by Albert Hoffman as active ingredient in morning glory seeds
- effects are extremely similar to LSD
- potency is ~10x-30x less than LSD
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Term
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Definition
- extracted from resin of bark of Central and South American trees and nuts
- ROA - usually inhaled as snuff; no effect if taken orally
- short duration; much less potency than LSD
- 30mg inhaled can result in acid effects w/in 10 seconds w/ a peak @ 10-15 minutes;
- lasts only one hour
- "businessman's lunch"
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Term
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Definition
- found in animals and plants
- skin of certain toads and Central and South American beans
- strong sympathetic activity
- much stronger than LSD, making it an unpopular street drug as strong sympathetic activity can feel like anxiety - unpleasant
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Term
| Ibotenic Acid and Ibogaine |
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Definition
- Ibotenic Acid
- found in amanita muscaria mushroom
- one of the world's oldest intoxicants dating
- it is believed that Viking warriors (beserkers) took ibotenic acid before going into battle
- Ibogaine
- found in iboga root in Africa
- acetylcholine muscarinic receptor agonist
- increase parasympathetic activity
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Term
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Definition
- atropine from belladona berry (deadly nightshade) and other plants
- these are anticholinergic drugs - antagonists of acetylcholine receptors
- decreases parasympathetic activity
- increase in heart rate
- increase in blood pressure
- fevers
- psychologically, they induce delirium and confusion; also induce amnesia - probably why they are not popular
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Term
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Definition
- known as dissociative anesthetic - even though awake, the person appears disconnected from environment
- technically, it is a synthetic depressant - was first taken as a pill PO; now taken in powdered or liquid form
- added to cigarettes or marijuana
- low doses (1-5 mg) produce drunken state, euphoria, numbness in hands and feet
- 5-15 mg induce analgesia and anesthesia, confusion, impairment of ability to communicate, rigid body position (catalepsy)
- larger doses induce psychoses
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Term
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Definition
- insensitivity to pain (even though the person is awake)
- increases blood pressure
- increases heart rate
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Term
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Definition
- distortions in body images
- feelings of depersonalization
- sense of timelessness
- transient feelings of being in outer space, dead, or not having arms or legs
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Term
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Definition
- act as channel blocker for a subtype of NMDA Receptor
- prevents Ca2+ and Na+ from flowing into the neuron
- accounts for some behavioral effects, but psychoses probably induced by affecting the dopamine system (preventing dopamine reuptake)
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Term
| Hallucinogens as a Model of Psychosis |
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Definition
- one of the earlier goals for LSD was to use it as a model for psychosis - this is true of other hallucinogens as well
- LSD and Schizophrenia
- very different
- w/ LSD hallucinations are visual and usually pleasant and experience concerned w/ interpersonal relationships
- w/ schizophrenia hallucination are largely auditory and threatening or unpleasant and there is lack of concern about interpersonal relationships
- schizophrenics in remission who take LSD have noted that they are different psychotic states
- PCP and Schizophrenia
- very similar
- characterized by global paranoia, auditory hallucinations, and ambivalence towards friends
- also rigidity, delusions of persecution and grandeur
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Term
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Definition
- developed as an anaesthetic in 1965; discontinued as an anaesthetic in humans, due to psychological side effects; continues to be used as a veterinary anaesthetic
- synthesis is complicated ‑ majority comes from thefts from vets offices
- ROA
- oral
- nasal
- intravenous
- intramuscular injection
- powder can be sprinkled on tobacco or other smokable materials
- effects begin to be felt after 20 minutes (oral), 5‑10 minutes (nasal) or almost immediately (injection)
- effects persist for 1‑6 hours and 24‑48 h are required to completely recover
- antagonist of NMDA receptor (not blocker like PCP)
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Term
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Definition
- effects are similar to PCP
- hallucinations ‑ blocks normal thinking, memory recall and most sensory input; in the absence of external input, the brain tends to fill the void with a "new reality“
- "Out‑of‑body experience" ‑ your mind dissociates itself from your body
- detachment from reality
- paranoia
- disorganized thinking
- loss of motor control (difficulty in walking, standing and talking)
- memory loss
- numbness
- drowsiness
- nausea
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Term
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Definition
- derived from peyote cactus plant
- found in wide area ranging from northern South America to southwestern US
- ROA - usually taken orally
- effective dose is 200mg
- peak response 30min - 2hrs after consumption
- physiological and psychological effects very similar to LSD - in double-blinds subjects can't tell difference
- very similar in structure to norepinephrine and dopamine
- likely agonist for catecholamine receptors
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Term
| 2,5-dimethoxy-4-methylamphetamine - (DOM) |
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Definition
- similar in structure to mescaline and amphetamine
- 80x more potent than mescaline but much less than LSD
- 3-5 mg produces euphoria; 10 mg or more, severe hallucinations
- far higher incidence of panic attacks, acute psychoses
- stimulant effects less than amphetamines
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Term
| 3,4-methylenedioxymethamphetamine - (MDMA) |
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Definition
- similar to amphetamine and mescaline in structure
- has the stimulant qualities of amphetamine as well as the hallucinogenic qualities of mescaline
- many effects are similar to LSD, although the psychological effects appear to be largely positive
- negative effects are mostly physiological - very high blood pressure, muscle tension, sweating, blurred vision, loss of motor coordination
- ROA
- most commonly taken orally
- some reports of it being injected
- effects usually begin 30‑60 minutes after oral administration
- effects usually last for 3‑4 hours, peaking after about 1‑2 hours
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Term
| Tolerance and Withdrawal with MDMA |
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Definition
- most users of MDMA report that after multiple exposures the positive effects of the drug are not as pronounced
- a 'hangover' effect may occur after using ecstasy that includes some or all of the following symptoms: insomnia, depression, fatigue, and difficulty concentrating
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Term
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Definition
- in animal studies MDMA has been shown to destroy monoamine (dopamine, norepinephrine and serotonin) neurons
- PET Imaging study ‑ MDMA users showed decreased global and regional brain serotonin transporter binding compared with controls
- Decreases in monoamine transporter binding positively correlated with the extent of previous MDMA use
- Death can result under three distinct circumstances after ecstasy is taken
- the stimulant effect
- results in heart attack or brain hemorrhage
- overheating
- the combination of taking ecstasy with prolonged and vigorous dancing raises the body temperature to dangerous levels
- some users have died from heat stroke
- over‑drinking
- it is important not to drink too much water, all at once
- several deaths have occurred from dilutional hyponatremia
- a condition where a person's brain literally drowns from the excess fluid intake
- brain also swells due to the hypo‑osmolarity
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Term
| MDMA effects @ cellular level |
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Definition
- blocks the reuptake of dopamine and serotonin (blocks the transporters)
- dopamine and serotonin releasing action
- agonists at norepinephrine and dopamine receptors
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Term
| Monoamine Hallucinogen PNS Effects (DOM, Mescaline, MDMA) |
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Definition
- PNS Effects
- Increase sympathetic autonomic nervous system activity:
- dilate pupils
- increase blood pressure
- increase heart rate
- increase body temperature
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Term
| Monoamine Hallucinogen Tolerance (DOM, Mescaline, MDMA) |
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Definition
- Fairly rapid tolerance to mental and sympathetic effects
- Tolerance appears to be complete after 3-4 daily exposures
- Cross-tolerance to each other
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Term
| Anxiety vs. Fear vs. Phobia |
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Definition
- anxiety
- apprehensive anticipation of future danger
- experienced as dysphoric (unpleasant)
- accompanied by somatic symptoms (e.g. muscle tension)
- fear
- more appropriate term to use when
- real threat or danger exists
- when referring to animals as we don't know their state of mind
- phobia
- Persistent, excessive or irrational fear of specific object, activity or situation
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Term
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Definition
- Cognitive appraisal
- Recognize and remember real threat
- Physiologic arousal
- Signal danger
- Enhance alertness
- Prepare body for action
- Behaviors
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Term
| When Anxiety Becomes Pathological |
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Definition
- Pathological anxiety occurs when safe stimuli (e.g., situations, objects) acquire a meaning of danger
- Anxiety is excessive, inappropriate or generalized
- Responses to feared stimuli are maladaptive
- Becomes a Disorder when source of significant subjective distress or functioning impaired
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Term
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Definition
- Panic Attacks: A Symptom
- Not specific to Panic Disorder
- Occurs in social phobia, PTSD and OCD
- sudden and rapid onset of intense fear accompanied by somatic symptoms similar to those of heart attack
- Panic Disorder:
- Recurrent unexpected panic attacks
- Followed by one or more of the following:
- Anticipation of additional attacks
- Worry about implications of attacks
- Change in behavior
- With or without Agoraphobia
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Term
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Definition
- Fear of open spaces
- Anxiety about being in situations from which escape might be difficult
- Often secondary to panic attacks
- Avoids: driving, bridges, tunnels, elevators, airplanes, malls, long lines, sitting in middle of row, etc.
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Term
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Definition
- Significant fears of situations where the person may be scrutinized by others, or embarrassed in a public situation
- Fear is that you’ll do something to cause embarrassment
- Exposure to the feared situation almost invariably provokes anxiety (sometimes panic attacks)
- Person has insight into excessive nature of fear
- Feared situations are often avoided
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Term
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Definition
- Persistent, irrational fears of objects or situations
- Common in general population: up to 5% of men, 10% women
- Rarely cause sufficient impairment or distress to warrant diagnosis of Disorder
- Examples:
- Animals:
- Snakes (ophidiophobia)
- Spiders (arachnophobia)
- Dogs (cynophobia)
- Objects:
- Situations:
- Heights (acrophobia)
- Closed (claustrophobia)
- Flying (aerophobia)
- Dentist (dentophobia)
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Term
| Obsessive Compulsive Disorder |
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Definition
- Recurrent unwanted, distressing thoughts (obsessions) and/or repetitive irresistible behaviors (compulsions).
- Majority have both.
- Insight present: acknowledged as senseless or excessive at some point during illness.
- Compulsions usually reduce anxiety but are not pleasurable.
- Symptoms produce subjective distress, are time-consuming (>1hr/day), or interfere with function.
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Term
| Generalized Anxiety Disorder |
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Definition
- Excessive worries about real life problems such as school and work performance.
- Typically seek help for somatic concerns
- Women > men
- One year prevalence of 3 - 4%
- Prevalence in primary care setting of 8%
- Accompanied by anxiety symptoms
- 3 or more of the following:
- Restlessness or feeling keyed-up or on edge
- Easy fatigability
- Trouble concentrating
- Irritability
- Muscle tension
- Sleep disturbance
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Term
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Definition
- Exposure to a traumatic event with:
- Serious risk of death or dismemberment to self/others
- “battle fatigue”
- Their response is key. Must involve:
- Intense fear
- Helplessness
- Horror
- The traumatic event is persistently reexperienced (dreams, hallucinations, flashbacks, etc)
- Person avoids reminders of the trauma
- May experience a numbing of emotions
- Chronic state of hyperarousal
- Must last more than 1 month
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Term
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Definition
- increased Locus Coeruleus activity (norepinephrine)
- decreased Raphe Nucleus activity (serotonin)
- increased amygdala
- process sensory info and assigns emotional valence
- hippocampus important in stored memories
- hyperactive hypothalamus
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Term
| How can we study anxiety? |
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Definition
- Lesion different areas in animals: fearful?
- bilateral amygdala lesion leads to Kluver-Bucy Syndrome - reduction/lack of fear and anxiety
- Record from different brain regions during exposure to fearful stimuli
- amygdala responds to the size of the whites of peoples eyes - can tell difference between fear and happy
- Expose people to fearful stimuli and do brain imaging
- Give drugs that affect or mimic neurotransmitters and look at behaviors
- locus coeruleus foot shock test
- mice spend less time in open arm when administered MAO inhibitors and yohimbine autoreceptor antagonist for NE neurons
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Term
| Treatments and Targets of Anxiolytics or Depressants |
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Definition
- Treatments
- alcohol - oldest sedative
- barbiturates - danger of overdose
- benzodiazepines - highly prescribed beginning in 1970s
- Targets/Factors Implicated in Treatments
- Neurochemicals
- Central: NE, 5HT, GABA
- Peripheral: Release of ACTH (pituitary), adrenal cortisol (adrenal cortex) and NE and epinephrine (adrenal medulla)
- Neuroanatomical areas
- Locus Coeruleus (increased NE firing)
- Amygdala (increased sensitivity to sensory stimuli)
- Hypothalamic Pituitary Axis (HPA) activation
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Term
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Definition
- more than 2000 compounds with the same basic structure
- developed in 1864 by Bayer
- by 1903 were being used to treat insomnia
- later used to reduce aggression and decrease anxiety
- very low therapeutic index
- CNS Effects
- CNS Depressant
- primarily used to induce sleep
- not normal sleep
- reduce REM sleep
- stopping use results in "rebound" REM sleep - enhanced REM sleep (longer)
- reinforcing to animals (they will self-administer it)
- respiratory depression (can be fatal)
- overdose is most serious acute risk
- too high a dose
- SYNERGISM
- alcohol + barbiturates
- 1/2 lethal dose of secobarbital + 1/4 lethal dose of alcohol
- 1973-76
- accounted for half of all drug-related suicide
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Term
| Pharmacodynamics of Barbiturates |
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Definition
- Barbiturates enhance GABA receptor activity - GABAA receptors
- noncompetitive agonist
- results in the opening of Cl- channel
- entry of Cl- into the cell
- prolongs the duration of the channel being open
- results in hyperpolarization of neuron - less excitable
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Term
| Tolerance, Dependence, and Withdrawal For Barbiturates |
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Definition
- metabolic tolerance: increases the production of the enzymes in liver that break it down
- cross-tolerance with alcohol
- dependence is most likely at doses above 400 mg (twice the hypnotic dose)
- could get there because of tolerance
- extreme tolerance to sleep effects w/ no tolerance to overdose
- Withdrawal
- @ low doses
- anxiety
- nausea and vomiting
- insomnia
- muscle tremors ("shakes)
- REM sleep rebound
- @ high doses/abrupt withdrawal
- similar to alcohol as it is sedative hypnotic w/ low therapeutic index
- psychosis (DTs)
- seizures
- cardiac arrhythmias
- can be fatal
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Term
| Pharmacokinetics of Benzodiazepines |
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Definition
- Most benzodiazepines are metabolized into active metabolites –
- probably a reason for their long-duration of action – half-life is a few hours
- metabolites are active for up to 20 hours
- **Benzodiazepines that are highly lipid-soluble and do not form active metabolites are often used for sleeping disorders because they have a faster onset of action, but do not interfere with activities the next day
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Term
| Benzodiazepines vs. Other Anxiolytics |
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Definition
- Absorbed more slowly
- High therapeutic index - very few deaths from overdoses, unless they are used in combination with other sedatives
- Minimal anesthetic effects
- Less effects on REM sleep
- Minimal effects on hepatic enzyme system - do not enhance the hepatic metabolism of themselves or other drugs
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Term
| CNS Effects of Benzodiazepines |
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Definition
- Effects are very similar to barbiturates
- Decreases in excitatory neuronal activity in cortex, limbic system, RAS
- Due to increases in inhibition in these areas
- Difference - seems to decrease hypothalamus activity
- hypothalamus - regulates many parts of the autonomic nervous system through release of hormones
- Decrease in activity results in decrease in the sympathetic nervous system
- This is probably why benzodiazepines are effective as anxiolytic drugs
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Term
| Cellular Effects of Benzodiazepines |
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Definition
- more specific activity to enhance the activity of endogenous GABA
- specific because there are highly specific benzodiazepine binding sites on the GABA receptors: cortex, limbic structures, cerebellum
- They are indirect GABA agonists
- bind to sites on GABAA receptors that are different from the GABA binding site
- effect: increase the ability of GABA to bind to its receptors and also increase its effects once bound
- results in enhancement of Cl- flow into neurons
- negative ions result in hyperpolarization and loss of neuronal excitability because they are indirect agonists, the effects depend on GABA concentrations
- low GABA concentrations they produce large effects
- high GABA concentrations they produce minimal effects
- lack of effect on maximal responses may account for lower toxicity of benzodiazepines (hard to overdose)
- do not by themselves activate the GABA receptor (different from barbiturates)
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Term
| Tolerance to Benzodiazepines |
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Definition
- Some tolerance develops, varies for different effects
- slow tolerance to anti-anxiety effects
- fast tolerance to sedative effects
- Benzos do not have a strong effect on the hepatic enzyme system
- Withdrawal symptoms lessened
- Chronic exposure leads to GABA receptor down-regulation and desensitization (not to same extent as it would be if there were strong metabolic tolerance)
- Therefore, more benzodiazepine is needed to have the same effect
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Term
| Dependence and Withdrawal of Benzodiazepines |
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Definition
- Dependence on benzodiazepines is not as strong as for barbiturates
- Because enzyme system is not upregulated, perpetually higher doses of drug are usually not necessary
- However, some dependence can still develop, why?
- Loss of coping mechanisms aside from drug use
- Abuse of drugs for avoidance of stressful situations
- Abuse as “downers” to come off high, counteract side effects of stimulant drugs such as cocaine, amphetamine
- Withdrawal
- Acute cessation leads to withdrawal symptoms associated with hyperactivity(similar to anxiety)
- gradual decline in usage recommended
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Term
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Definition
- liquids that vaporize @ room temp found in variety of inexpensive, accessible products including:
- paint thinners and removers
- dry-cleaning fluids
- degreasers
- gasoline
- glues
- correction fluids
- felt-tip markers
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Term
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Definition
- sprays containing propellants and solvents and also include accessible products like:
- spray paints
- deodorant and hair sprays
- vegetable oil sprays for cooking
- fabric protector sprays
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Term
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Definition
- include medical anesthetics as well as gases used in household or commercial products.
- Medical anesthetics include ether, chloroform, halothane, and nitrous oxide (commonly called "laughing gas").
- Nitrous oxide is the most abused of these gases and can be found in whipped cream dispensers and products that boost octane levels in racing cars.
- Other household or commercial products containing gases include butane lighters, propane tanks, and refrigerants.
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Term
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Definition
- act primarily to dilate blood vessels and relax muscles
- while most other inhalants are used to alter mood, nitrites have common usage as sexual enhancers
- include cyclohexyl nitrite, isoamyl nitrite, isobutyl nitrite
- commonly referred to as poppers or snappers
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Term
| Inhalant Routes of Administration |
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Definition
- "sniffing" or "snorting" fumes from containers
- spraying aerosols directly into the nose or mouth
- "bagging" — sniffing or inhaling fumes from substances sprayed or deposited inside a plastic or paper bag
- "huffing" from an inhalant-soaked rag stuffed in the mouth
- inhaling from balloons filled with nitrous oxide
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Term
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Definition
- Inhalant drugs involve a diverse group of chemicals that are generally either
- inhaled solvents
- inhaled anesthetics
- nitrous oxide
- inhalant chemicals are synthesized, not naturally-occurring
- generally found in common household items
- can be obtained legally and inexpensively
- most popular among older children/young adolescents for their easy access
- usage actually goes down w/ age as alcohol and marijuana go up
- can be first drug tried by kids for many
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Term
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Definition
- This category is a “wastebasket” of anything that can be inhaled and does not fall into one of the other inhalant categories
- Effects are somewhat like alcohol and anesthetics
- Inhalants are highly toxic and very dangerous
- Due to loss of muscular coordination and the flammability of inhalants, ~25% of deaths from inhalant use are due to accidents
- ~20% of deaths from inhaled solvents were first-time users
- ~25% of deaths from inhaled solvents are suicides
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Term
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Definition
- Used in surgery for their anesthetic properties
- Modern anesthetics are nonflammable and only require small amounts breathed in with air
- low margin of safety between anesthesia and death making them extremely dangerous for any usage outside doctor supervision
- Affect breathing, blood pressure, heart contractions
- It is not known why anesthetics work, especially why they suppress consciousness
- One effect on the brain is to enhance the effects of GABA
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Term
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Definition
- otherwise known as laughing gas
- Can suppress pain, but not cause deep anesthesia
- Used in dentistry
- Can be dangerous if user does not get enough oxygen, or if it is combined with other drugs
- Abuse
- Nitrous oxide can be abused to get a euphoric high
- It can be inhaled from small canisters (“whippets”) or from canisters that use nitrous oxide as a propellant
- Of the inhalants, is probably the “safest” because it does not affect critical body functions such as breathing
- There is a suggestion it can cause neurotoxic damage
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Term
| Behavioral Effects of Inhalants |
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Definition
- Moderate exposure:
- often compared to alcohol intoxication (including euphoria, disinhibition, lightheadedness)
- Heavier exposure:
- stronger depression of nervous system function
- slurred speech
- poor coordination
- sensory distortions including hallucinations and delusions (such as the delusion that one can fly)
- Very high exposure:
- anesthesia
- loss of consciousness and coma
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Term
| Pharmacokinetics and Pharmacodynamics of Inhalants |
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Definition
- It is not completely understood how inhalants have their effects
- Different types of inhalants do not necessarily do the same things to the brain and only really have in common that they are inhaled
- Rapidly absorbed from lungs into the bloodstream
- High lipid-solubility, so cross the blood-brain barrier easily
- Depressant effects are due in part to enhancement of GABA-A receptors, inhibition of NMDA glutamate receptors, and inhibition of nicotinic acetylcholine receptors
- Note that these neurochemical effects are somewhat similar to those of alcohol
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Term
| Health Risks of Inhalants |
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Definition
- unlike w/ many other drugs, inhalants can be easily fatal w/ first-time use
- “Sudden sniffing death syndrome”: death due to loss of normal heart rhythm
- Inhalants damage the heart, liver, kidneys, lungs, and bones
- Due to the high degree of lipid solubility, inhalant molecules can accumulate in myelin in both the brain and the peripheral nervous system - myelin damage!!
- Inhalant abusers can show longer-term cognitive impairments
- Fetal solvent syndrome: exposure during pregnancy (either abuse or on-the-job exposure) can cause birth defects, premature birth, low birth weight
- Very dangerous when combined with anything that causes sleepiness (such as alcohol, opiates, anti-anxiety drugs, and some cold medicines, including anti-histamines)
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Term
| Why are Inhalants and other CNS-depressants so dangerous? |
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Definition
- Medulla: Controls “primitive” functions such as breathing, heart rate, digestion, blood pressure
- A relatively small group of neurons located mainly in the medulla (the junction between the brain and spinal cord) control breathing
- If the activity of these neurons decreases, breathing will slow until the body does not get sufficient oxygen to stay alive
- The effects of multiple depressants can add up to cause breathing to stop before any individual drug would
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Term
| Duration of action, withdrawal, and dependence from inhalants |
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Definition
- Because intoxication lasts only a few minutes, abusers frequently seek to prolong the high by inhaling repeatedly over the course of several hours, which is a very dangerous practice.
- With successive inhalations, abusers can suffer loss of consciousness and possibly even death.
- After heavy use of inhalants, abusers may feel drowsy for several hours and experience a lingering headache.
- dependence
- A strong need to continue using inhalants has been reported by many individuals, particularly those who have abused inhalants for prolonged periods over many days
- Compulsive use and a mild withdrawal syndrome can occur with long-term inhalant abuse
- Therefore…mild physical dependence and potentially strong psychological dependence
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Term
| How do Inhalants Produce their effects? |
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Definition
- Nearly all abused inhalants (other than nitrites) produce a pleasurable effect by depressing the CNS
- Nitrites, in contrast, dilate and relax blood vessels rather than act as anesthetic agents
- Evidence from animal studies suggests that inhalants have mechanisms of action similar to those produced by CNS depressants (like alcohol and sedatives)
- A 2007 animal study indicates that toluene, a solvent found in many commonly abused inhalants activates the brain’s dopamine system.
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Term
| Short-term effects of Inhalants |
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Definition
- Most inhalants produce a rapid high that resembles alcohol intoxication
- Initial excitation followed by drowsiness, disinhibition, lightheadedness and agitation
- Almost all solvents and gases produce anesthesia and loss of sensation in sufficient quantities.
- Other effects include
- Apathy
- Belligerence
- Impaired judgments
- Nausea
- Vomiting
- Confusion
- Delirium
- Dizziness
- Slurred speech
- Dressed reflexes
- General muscle weakness
- Inability to coordinate movements
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Term
| Damage caused by long-term usage of inhalants |
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Definition
- the most significant toxic effect of chronic exposure to inhalants is widespread and long-lasting damage to the brain
- Damage to myelin
- Neurological syndromes that reflect damage to parts of the brain involved in controlling cognition, movement, vision, and hearing
- Cognitive abnormalities can range from mild impairment to severe dementia.
- brain scans even show effects similar to those seen w/ severe alcoholism and schizophrenia
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Term
| GHB - gamma-hydroxybutyrate |
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Definition
- Synthetic compound developed for medical purposes but none were fouond
- Marketed in 1980’s by health food stores as a nutritional supplement for bodybuilders
- No evidence for manufacturer’s claims that it would release hormones that would increase muscle mass and reduce body fat
- Banned by FDA in 1990
- current use is recreational
- FDA restrictions are circumvented by selling kits for synthesizing it at home from a chemical precursor
- Like ecstasy and ketamine, is often used at nightclubs and raves
- Colorless and odorless; sold as powder or as a solution in water
- Is intoxicating and, at sufficient doses, can be heavily sedating, so it can be used as a “date rape” drug
- ROA: most commonly ingested as solution where it is easily absorbed through GI tract
- crosses BBB easily
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Term
| Effects and Toxicity of GHB |
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Definition
- Low doses: alcohol-like experience: mild euphoria, relaxation, social disinhibition
- Higher doses: sleepiness, slurring of speech, difficulty in controlling movements such as walking), nausea, vomiting
- Overdose: memory impairment, depressed breathing, decreased heart rate, coma, seizures
- Extremely high overdose risk if combined w/ alcohol and other CNS depressants
- Routine screens in ER for toxic substances are not generally set up to detect GHB, so it is critical to inform medical personnel of use
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Term
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Definition
- very similar structure to GABA
- acts as agonist @ some GABAA receptors and as a block for some types of glutamate receptors
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Term
| GHB Tolerance, Dependence, and Withdrawal |
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Definition
- tolerance can develop as users go on binges to "chase the high"
- dependence
- Often, users become dependent because they use GHB recreationally, then as a way to get to sleep, and develop such a tolerance that they need to take GHB every few hours 24/7 and cannot sleep without it
- Withdrawal
- Can be unpleasant and start within a few hours
- Symptoms include insomnia, anxiety, sometimes psychosis, tremors, agitation, high heart rate and blood pressure
- Often withdrawal cannot be accomplished without medical help - like alcohol
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Term
| Potential Medical Uses of GHB |
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Definition
- Can be used to treat narcolepsy (extreme sleepiness and tendency for loss of muscle control)
- Treatment for alcoholism: helps prevent withdrawal symptoms and helps prevent relapses (only approved for this in a few European countries)
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Term
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Definition
- benzodiazepine used legally in Europe and Mexico as a sleep-inducing drug
- readily available on black market as a date rape drug
- also known as roofies or roche
- typically colorless when dissolved in alcoholic beverage
- can cause anterograde amnesia - or inability to store memories while on drug
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Term
| New Safety Measures for Date Rape Drugs |
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Definition
- Rohypnol made so that it turns blue when dissolved
- GHB and ketamine can be detected w/ coasters and test strips - but not Rohypnol
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