#41: GHB: Party Drug or Narcolepsy Treatment?
The double-edged sword of GHB’s mechanism of action
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GHB: Party Drug or Narcolepsy Treatment?
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GHB: Party Drug or Narcolepsy Treatment?
Jazz Pharmaceuticals, a leading global biopharmaceutical company, recorded an astonishing $1.8 billion in revenue this year from the sales of Gamma Hydroxybutyrate (GHB).
Xyrem® and Xywav® are the trade names of the Food and Drug Administration (FDA)-approved prescription medication versions of GHB approved as a treatment for narcolepsy and manufactured by Jazz.
Narcolepsy is a long-term neurological disorder that impairs the brain's ability to regulate sleep-wake cycles.
It can cause severe disruptions to a person's life, manifesting symptoms like excessive daytime sleepiness, sleep paralysis, hallucinations, and in some cases, cataplexy — a sudden loss of muscle control and strength.
Xyrem® and Xywav® are primarily prescribed to improve daytime sleepiness and muscle weakness associated with narcolepsy.
The substantial revenues raise some intriguing questions about the complex landscape of stigmatized psychoactive drugs, and GHB’s mechanism of action, and reputation.
Mechanism of Action
GHB is categorized as a central nervous system (CNS) depressant. Its effects include euphoria, drowsiness, decreased anxiety, confusion and memory impairment.
GHB can also produce both visual hallucinations and paradoxically, excited and aggressive behavior. GHB greatly increases CNS depressant effects of alcohol and other depressants.
Its mechanism of action, while not entirely understood, is believed to function by stimulating the GABA receptor in the brain, a primary inhibitory neurotransmitter that slows down brain activity. This action results in a deep sleep state, which helps people with narcolepsy get the restorative sleep they require but often struggle to achieve.
The dosing of Xyrem® (GHB) is a carefully managed process. It is usually given in two nightly doses, starting with a lower dose to assess patient tolerance, and then gradually increased to therapeutic levels as tolerated. The total nightly dose ranges from 6 to 9 grams, divided into two doses. The first dose is typically taken at bedtime, and the second dose is taken 2.5 to 4 hours later.
As with any medication, the benefits of Xyrem® must be balanced with its potential risks. Side effects may include nausea, bedwetting, breathing problems, confusion, and depression, among others.
Due to its depressant effects on the CNS, it can also be dangerous when combined with other CNS depressants, including alcohol. The potential for misuse and physical dependence adds to the need for careful prescribing and monitoring.
GHB’s Complex Reputation - 'Party Drug' & ‘Date Rape Drug’
GHB's role in successfully treating narcolepsy is less well known compared to its public reputation as a "party drug" and, more infamously, as a "date rape drug."
In non-medical settings, GHB has been misused for its euphoric and sedative effects, which can induce a state of relaxation and increase sociability. This makes it appealing in party or club scenes.
However, it's the drug's potent sedative properties, which can cause blackouts at higher doses, that have led to its misuse as a date rape drug.
These illicit uses have garnered GHB considerable negative publicity, and in many places worldwide, possession, supply, and production of this substance is considered illegal. GHB was placed on Schedule I list of the Controlled Substances Act in March 2000 in the USA.
GHB's dual identity as a very effective treatment for narcolepsy patients on one hand and a potentially dangerous recreational drug on the other, has raised a complex dilemma in the field of medicine and public health.
While GHB is a Schedule I substance, when sold as FDA-approved GHB products (such as Xyrem®), it is considered Schedule III, one of several drugs that are listed in multiple schedules.
Schedule I drugs are defined as “Drugs with no current medical use with high potential for abuse and/or addiction.”
Schedule III drugs are “Drugs with low to moderate potential for abuse and/or addiction, but less dangerous than Schedule I or II. These drugs can be obtained through prescription, but generally are not available over the counter.”
For the same molecule to exist in two schedules is surprising, and brings into question the Scheduling system defined by the Controlled Substances Act of the 1970s.
This dichotomy surrounding GHB points to the larger issue of the need for comprehensive drug education and regulation, focusing not just on the potential misuse but also on their therapeutic potential.
GHB can serve as an example of a controversial drug with therapeutic uses striving to ensure societal safety, as new psychedelics receive FDA-approval for medical uses.
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