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Lecture 21 in Psychology 2028 discusses the drug class known as sedative hypnotics, concluding the previous discussions on anxiolytics.

Older Compounds: Previously discussed anxiolytics included compounds like chloral hydrate, which have historical significance in the management of anxiety.
Barbiturates: The modern age of pharmacological management of anxiety began with the development of barbiturates, which have also been subject to recreational use.

Definition: Benzodiazepines are a class of drugs primarily used for the control of anxiety and historically for sleep, although their use for sleep is less common today.
Key Figure: Leo Sternbach is credited with the discovery and synthesis of the first benzodiazepines in the late 1950s. He was a postdoctoral researcher in Poland who initially developed several compounds for anxiolytic testing but halted the research due to lack of promising results.
First Benzodiazepine: One significant compound, identified as RO 5069, was found to have anxiolytic potential. It was marketed as Chlordiazepoxide, commercially known as Librium.
Second Benzodiazepine: Shortly after, Diazepam was developed and became widely recognized under the trade name Valium.
Minor vs Major Tranquilizers: Benzodiazepines are classified as minor tranquilizers; they provide calming effects and alleviate anxiety. This distinguishes them from major tranquilizers (antipsychotics), which are used to sedate individuals in severe agitation or psychosis.

Benzodiazepines undergo various screening tests to assess their potential as anxiolytics, focusing on psychological processes.

Apparatus Explained:
- The elevated plus maze consists of two open arms and two closed arms in an elevated position, mimicking fear-inducing environments for rats.
- Procedure: Rats are placed in the maze, and their time spent in open versus closed arms is measured over a specified duration (e.g., 20-30 minutes).
Expected Behavior: Typically, non-drugged rats spend more time in the closed arms due to fear of open spaces, indicating anxiety.
Drug Effects: An anxiolytic drug will increase the time spent in the open arms, suggesting reduced anxiety and discomfort in open spaces.
Findings: Research shows a dose-response relationship, where higher doses of Diazepam result in increased time spent in the open arms, demonstrating anxiolytic efficacy.

Procedure Overview: The Geller Sifter assesses behavior under two schedules of reinforcement in a controlled environment involving an animal model (often rats).
Multiple Schedule of Reinforcement:
- Involves presenting a red light indicating a Variable Interval (VI) schedule of reinforcement and a green light indicating a Fixed Ratio (FR) schedule with a shock.
- VI Schedule: Animals receive food based on time intervals where they must press a lever to obtain food, which encourages steady behavior.
- FR Schedule with Shock: Animals can obtain food continuously by pressing a lever but will also receive shocks, thus creating an anxiety-inducing condition.
Predicted Behavior:
- Non-drugged rats stop responding during the FR schedule due to the threat of shocks (anxiety).
- An anxiolytic should enable them to overcome anxiety and continue pressing the lever.
Results: Rats given benzodiazepines demonstrate the release from punishment effect, where they resume pressing the lever despite being shocked, differentiating the anxiolytic effect from mere pain relief.

Benzodiazepines are classified based on their duration of action, which is not linked to lipid solubility but rather their specific drug characteristics.
Long-Acting Benzodiazepines:
- Chlordiazepoxide (Librium)
- Diazepam (Valium)
Intermediate-Acting Benzodiazepines:
- Lorazepam (Ativan) — Widely used today.
- Clonazepam (Klonopin) — Often paired with opiate use.
- Flunitrazepam (Rohypnol) — Known as a date rape drug.
Short-Acting Benzodiazepines:
- Midazolam (Versed)
- Oxazepam (Serax)
- Alprazolam (Xanax)
- Triazolam (Halcyon) — Previously popular but withdrawn due to adverse reactions.

Target Demographics: The primary users of benzodiazepines mirror those of barbiturates; often white, Caucasian, middle-aged, potentially stay-at-home housewives, reflecting broader historical patterns within the pharmacological landscape.
Cultural References: The lyrics of the Rolling Stones’ "Mother's Little Helper" reflect the prevalence of benzodiazepine use in this demographic.

Common Effects: Reduce anxiety, provide sedation, aid in muscle relaxation, and possess anticonvulsant properties. They decrease the latency to sleep onset and increase total sleep time, though tolerance to these sleep benefits develops over time.
Cognitive Deficits: Benzodiazepines can cause impairments in working memory, attention, and expressive language, particularly prominent in older adults. Health professionals need to monitor doses closely in older patients to prevent cognitive issues.
Anterograde Amnesia: Users may experience an inability to recall events following drug consumption, contributing to their potential misuse as date rape drugs.
Neurological Impact: These drugs modulate GABA receptors, enhancing inhibitory actions and creating risks when combined with depressants like alcohol.
Benzodiazepine Antagonist: Flumazenil is known for its role in reversing benzodiazepine overdose effects.
Tolerance Development: Common to effects including muscle relaxation, sedation, and anticonvulsant actions, but it may not develop as clearly for anxiolytic and amnestic effects, making the latter two potentially more suitable for medical use.

Withdrawal symptoms can manifest as excess neuronal excitability, seizures, agitation, and memory impairment, much like alcohol withdrawal.
Withdrawal Signs Include: Sleep disturbances, irritability, tremors, concentration difficulties, and in severe cases, seizures.

Definition: A naturally occurring neurotransmitter, GHB has sedative-hypnotic properties similar to benzodiazepines and barbiturates, but is distinct from both.
Effects: GHB can produce relaxation, mild euphoria, loss of consciousness, and amnesia; often referenced as "liquid ecstasy" and referred to in contexts involving sexual assault.
Manufacturing: Although marketed as safe, it is synthesized from common household products, negating its "natural" label.
Antagonism: The effects of GHB can also be counteracted by Flumazenil, suggesting similarity in mechanisms with GABA receptors relevant for both GHB and benzodiazepines.
Delivery Forms: GHB can be ingested in various forms (liquid, powder, or injected) and is sometimes surreptitiously administered in cases of drug-facilitated assault.

The lecture offers a comprehensive look at benzodiazepines, their historical context, testing mechanisms for anxiolytic potential, effects on cognition and behavior, and the implications of their use in various demographics, along with detailing GHB as a unique sedative-hypnotic.