Test 4: Drugs of Abuse pt 1 Flashcards
The economic burden of addiction is estimated at more than ___________ annually in the United States.
The economic burden of addiction is estimated at more than $400 billion annually in the United States.
What is addiction?
-Psychological dependence on a drug
-Compulsive drug use despite negative consequences
-Triggered by cravings and contextual cues
-Not the same thing as dependence (Dependence occurs with chronic exposure - only a small amount of users become addicted)
-Relapse is common even after successful withdrawal.
What is the brain pathway associated with addiction?
The Mesolimbic pathway (also referred to as the reward pathway)
-A Dopaminergic pathway
-Connects the Ventral Tegmental Area (midbrain) to the Nucleus Accumbens.
-Most significant neural pathway in the brain for addiction.
What is the Ventral Tegmental Area (VTA)?
Located in the midbrain
-Dopamine producing neurons
-Releases large quantities of dopamine to the nucleus accumbens and prefrontal cortex.
Systemic administration of drugs of abuse causes the release of dopamine.
What are the receptors associated with the 3 classes of addictive drugs?
1) GPCR
2) Ionotropic Receptors
3) Dopamine Transporter
What addictive drugs are included in Class 1 (GPCRs)?
-Opioids
-Cannabinoids
-Gamma-Hydroxbutyric Acid
-Lysergic Acid Diethylamide-25
-Mescaline (peyote)
-Psilocybin (mushrooms)
What is the MOA of the Class 1 drugs (GPCRs)?
Increased Dopamine due to inhibition of GABA.
Targets the GABA neurons of the VTA.
Inhibit neurons via:
-Post-synaptic hyperpolarization – K+ (harder to depolarize - receptor will not fire)
-Pre-synaptic regulation of transmitter release – Ca++ (can’t release NTs from the presynaptic membrane without Caclium)
Inhibit the inhibitors, resulting in excitation of the system.
What is the MOA of opioids?
-Target MORs in the VTA, located exclusively on GABA neurons
-Presynaptic inhibition of voltage-gated Ca channels
-Postsynaptic activation of K+ channels, causing K efflux and hyperpolarization
Together, the pre and post synaptic mechanisms reduce NT release and suppress activity, taking away the inhibition by the GABA neurons.
How do Cannabinoids work on a cellular level?
-Δ9-tetrahydrocannabinol (THC) and other cannabinoids mainly act through presynaptic inhibition. (CB1R, cannabinoid receptors)
-THC stimulates CB1 receptor to decrease release of GABA (indirectly increasing Dopamine)
How does Gamma-hydroxybutyric acid (GHB aka roofies) act on a cellular level?
-Gamma-hydroxybutyric acid (GHB) targets GABAB receptors, which are located on both cell types.
-However, GABA neurons are more sensitive to GHB than are DA neurons, leading to disinhibition at concentrations typically obtained with recreational use.
-Therapeutic use with Narcolepsy.
What drugs fall under Class 2 (Ionotropic receptors)?
Nicotine
Benzodiazepines
Barbiturates
Alcohol
Ketamine
Phencyclidine
Nitrates, ketones, hydrocarbons (inhalants)
What is the MOA of the drugs in Class 2 (Ionotropic)?
Direct release of Dopamine from neuron.
Ionotropic: Ligand gated ion channels
-Opened by something that will trigger the receptor.
-Weakly sensitive to RMP
-Combines the effects of Dopamine and GABA neurons
-Increases the release of Dopamine.
What drugs are in Class 3 (Dopamine Transporter)?
Cocaine
Amphetamines
What is the MOA of the drugs in Class 3 (Dopamine transporter)?
Increased Dopamine due to blocking of transporters.
-Block dopamine reuptake, allowing for more circulating dopamine in the system.
-Stimulate non-vesicular dopamine release (release of dopamine not stored as a vesicle)
-Also blocks cytoplasmic transporter and the transporter that puts it into a vesicle.
-Causes an accumulation of extracellular dopamine in the target structures = excitation.
-Also effects the transporters of other monoamines (NE and 5HT)
What are the beneficial effects of Cannabinoids? (Why used in medical therapies)
Increased appetite
Attenuation of nausea
Decreased intraocular pressure
Relief of chronic pain
What is decriminalization?
The legal consequences for possession of small amounts of pot are not severe and someone caught with a small amount of marijuana won’t face prosecution, jail time, or a receive a criminal record.
What is legalization?
The legalization of recreational marijuana means that adults can legally use, possess, and even grow their own marijuana for personal use.
What are Cannabinoids?
-Class 1 (GPCRs)
-Psychoactive substance = tetrahydrocannabinol (THC)
-Leads to dependence with chronic use
-Low risk for addiction (2/5)
What is the MOA of Cannabinoids?
Disinhibition of Dopamine neurons by presynaptic inhibition of GABA neurons of the VTA
What are the effects of Cannabinoids?
-Onset (smoking) within minutes
-Peak 1-2 hours
-Euphoria, relaxation, feelings of well being,
-Grandiosity, and altered passage of time
What effects can occur with higher doses of Cannabinoids?
-Visual distortions
-Drowsiness
-Diminished coordination
-Memory impairment (chronic use)
-Can create dysphoric state (chronic use).
Rare cases following very high doses:
-Visual hallucinations
-Depersonalization
-Psychotic episodes
What are withdrawal symptoms associated with Cannabinoids?
Mild, short duration (24-72 hours)
-Restlessness
-Irritability
-Mild agitation
-Insomnia
-Nausea
-Cramping
Who is most at risk for Heroin use?
-18-25 year old non-hispanic whites
-People in large metropolitan areas
-Incidence has increased in US due to increase in supply
-Amount in US quadrupled since 2000.
-Issue is approx. 50% are addicted to pain killers. Issue with prescription drug abuse.
What kind of drug is Heroin?
-Class 1 (GPCR)
-Semi-synthetic opioid agonist
-More potent than morphine
-Rapidly metabolized to morphine via biotransformation.
-More intense rush and more potent analgesia than morphine (More soluble, crosses BB Barrier more rapidly)
-Tolerance leads to death from respiratory depression
-Highly addictive (4/5)
What are the effects of Heroin?
A rush of euphoria followed by 2-4 hours of sedation (Blue Box)
What is Lysergic Acid Diethylamide-25 (LSD)?
An ergot alkaloid.
-Pschotomimetic & neurotoxic
-Does NOT stimulate dopamine release.
-Onset within 30 minutes, DOA 6-12 hours.
What are the effects of LSD due to it being psychotomimetic & Neurotoxic?
-Depersonalization
-Distorted time perception
-Strong hallucinogen
-Unpredictable changes in perception
What are the somatic symptoms associated with LSD?
Dizziness
Nausea
Paresthesias
Blurry vision
Has the potential to prolong the analgesic and respiratory depression effects of opioids.
What is the MOA of Lysergic Acid Diethylamide-25 (LSD)?
-Increase Glutamate release in the cortex (excitatory, stimulant)
-Enhancing the afferent input of the presynaptic serotonin receptors (5-HT2A) of the thalamus
-Induces tolerance
-Addiction potential is low.
