Biopsychological effects of drugs and alcohol

The ascending spinothalamic pathway transmits_____ signals to the brain. This information crosses the midline in the _____

pain (nociceptive); spinal cord

What is the primary mechanism of action for heroin, morphine, and fentanyl?

Mu opioid receptor (MOR) agonists

Buprenorphine is a therapy for opioid addiction. It works by:

Partial agonist at opioid receptors, reducing cravings and withdrawal while limiting euphoria

Which of the following describes the primary way that opioids produce their reinforcing effects?

Dopamine disinhibition (increase dopamine in nucleus accumbens)

Although some people begin taking a drug such as heroin solely for its euphoric (and/or other desired) effects, they may eventually take it to avoid withdrawal as well.  These processes are called:

positive and negative reinforcement

Tolerance to the effect of opioids on ____ develops rapidly and at relatively low doses, compared to other effects of the drug

euphoria and analgesia (pain relief)

The three symptoms of opioid overdose are:

Respiratory depression, pinpoint pupils, unconsciousness

Roughly what percentage of morphine is transformed by the liver into the active metabolite morphine-6-glucuronide (M6G)?

~10%

Treatment with “replacement drugs,” like methadone, can be beneficial for those recovering from heroin addiction because:

Long-acting agonist that prevents withdrawal and reduces cravings without strong euphoria

How do endorphins reduce pain sensations at the level of the spinal cord?

Inhibiting release of glutamate and Substance P and reducing postsynaptic activation

Which family previously owned the pharmaceutical company Purdue Pharma, and recently faced lawsuits regarding over-prescription of opioid drugs like Oxycontin, plus spreading misinformation that these drugs were not addictive?

Sackler family

Jesse smokes cannabis and, a little while later, feels extremely hungry (also known as the “munchies”). What is happening in Jesse’s body to cause the “munchies?”

Increased ghrelin + enhanced smell/taste sensitivity

According to the Hemp Farming Act of 2018, what is the highest level of delta-9-THC that is allowed in legal hemp?

0.3% delta-9-THC

Dr. Hank Schrader is developing an endocannabinoid-based drug that increases levels of anandamide (AEA) in the brain. What are some ways that Dr. Schrader’s drug might work to increase AEA?

Inhibit FAAH, block reuptake, increase release

Endocannabinoids play a role in regulating stress. In general, anandamide is ____ in response to stress, initiating the release of cortisol from the adrenal glands, which ____ 2-AG signaling in the brain, shutting down the stress response.

decreased; increases

The first cannabinoid drug dronabinol (Marinol®) was approved by the FDA as a Schedule III controlled substance for the treatment of:

Appetite stimulation and anti-nausea (chemotherapy patients)

Cannabidiol (CBD) reduces seizures in treatment-resistant epilepsy, likely through:

Anti-inflammatory and neuroprotective effects (modulating neural excitability)

Endocannabinoids act as retrograde neuromodulators, which means they:

Released postsynaptically and act on presynaptic neurons to inhibit neurotransmitter release

Deficient endocannabinoid signaling is associated with:

Anxiety, PTSD, impaired stress regulation

What psychophysiological effects has been reported after cannabis use?

Euphoria, relaxation, altered perception, increased appetite, impaired memory

There is a positive correlation between adolescent cannabis use and schizophrenia development in adulthood. What might be a reason why this relationship exists?

It doesn’t cause schizophrenia but cannabis can be a risk factor to set off schizophrenia

Describe the cellular mechanism of THC’s effects

Partial agonist at CB1 receptors → inhibits neurotransmitter release + increases dopamine

It appears that CBD counteracts some of the effects of delta-9-THC by acting as a:

Negative allosteric modulator of CB1

Which U.S. state was the first to legalize medical cannabis use in 1996?

California

Chronic MDMA use causes severe, long-lasting damage to ____ neurons. 

Serotonergic

The cellular mechanism of drugs like LSD and psilocybin is complicated because these drugs appear to:

Act as serotonin (5-HT2A) receptor agonists (and affect other systems)

Dissociative psychedelics like PCP and ketamine interfere with memory formation by:

Blocking NMDA (glutamate) receptors → disrupt LTP

What are some characteristics of PCP use?

Dissociation, hallucinations, aggression, psychosis, numbness, memory loss

What is the primary psychoactive ingredient in magic mushrooms?

Psilocybin

Hallucinogens like LSD, psilocybin, and MDMA have promising therapeutic effects for stress-related disorders like PTSD. What are some possible mechanisms by which these drugs produce these therapeutic effects?

Increase serotonin, promote neuroplasticity, reduce negative emotional salience

Is LSD addictive? Can you become dependent on LSD? Why are why not?

No physical dependence; very low addiction potential

Some common and potentially dangerous effects of MDMA in the settings in which it is typically used are:

Hyperthermia, dehydration, serotonin depletion (crash)

Skylar injects a drug; within minutes her eyes have a glassy stare, and she becomes disoriented and unable to think or communicate coherently; soon her body feels disconnected and “rubbery.” Later, Skylar has little memory of what occurred after she took the drug. Skylar most likely took:

Ketamine or PCP (dissociative)

Walter is at a party and is given a pill, which he takes. Within an hour, he begins to feel particularly good about who he is, about being at this party, and about being with his friends. He feels very “connected” to everyone, feeling for the first time that they truly understand him. For a few hours Walter also feels quite energetic and exhilarated, and occasionally notices some visual afterimages, “vibrations,” and size distortions. The pill that Walter took was probably:

MDMA (ecstasy)

Which of the following drugs was discovered by accident when chemist Albert Hofmann absorbed the drug through their fingers while studying the chemical properties of fungi?

LSD

Hallucinogens like LSD disrupt connectivity in the ____, which likely contributes to a temporary loss of a sense of self that is often produced by these drugs.

Default Mode Network (DMN)

PCP and ketamine produce alcohol-like physical effects by acting as:

NMDA receptor antagonists

MDMA acts as an entactogen, increasing empathy and social bonding. It does this primarily through:

Oxytocin release + serotonin increase

Some hallucinogens cause synesthesia, which is defined as:

Mixing of sensory experiences (e.g., “seeing sounds”)

Be able to identify which drugs that we discussed in this section would produce cross-tolerance if taken together

Alcohol + opioids

Opioids + benzodiazepines

Opioids + barbiturates

Withdrawal symptoms of opioids

Pain, sweating, nausea, diarrhea, anxiety

Withdrawal symptoms of Cannabis

Irritability, sleep issues, appetite loss, anxiety

Withdrawal symptoms of MDMA

Depression, fatigue, low motivation

Withdrawal symptoms of Psychedelics (LSD)

No significant withdrawa

dose response curve based on efficacy and potency

Potency: how much drug needed (left = more potent)

Efficacy: maximum effect (higher curve = greater efficacy)