GHB

GHB is gamma-hydroxybutyrate (or gamma-hydroxybutyric acid):

It is produced endogenously in the body, and agonizes a couple of receptor types in the brain:

• GHB receptors, which are apparently not well understood, but can have excitatory activity including leading to increased concentrations of glutamate, and also
• GABA_B receptors, where GHB is only a mild agonist.

GHB itself is a precursor to both glutamate and GABA, which are the major excitatory and inhibitory neurotransmitters, respectively.

A plausible model of GHB activity is that recreational (high) doses of GHB are sufficient to activate GABA_B receptors, giving them a primarily depressant effect, but that falls away as the drug is metabolized and at lower concentrations the excitatory effects from the GHB receptors dominate. This explains why people who take GHB as a sleep aid often 'rebound' and wake up after a few hours.

Recreational use

GHB seems to have many of the same subjective effects as ethanol: people feel euphoric, disinhibited, socially engaged, even sexually aroused, all without the calories, sleep disruption, hangover, or toxic metabolites. This makes GHB seem like a pretty attractive substitute for alcohol.

What are the downsides? My mental model is that using GHB 'like alcohol' is probably safe: the associated dangers of overdose, dependence, etc. are pretty similar in character and magnitude. However, it may be easier to screw up, because GHB doses are smaller and it's not self-limiting the way that alcohol often is.

Specific concerns include:

Overdose: GHB is very dose-sensitive. Typical recreational doses are 1-3g, while doses above 4-6g can lead to rapid unconsciousness,This is the source of GHB's reputation as a 'date rape' drug. It should go without saying that one should never give people drugs, or have sex with them, without their knowledge and consent. and significantly higher doses may lead to respiratory depression and even death (this seems pretty rare for people taking GHB alone, but it's certainly possible). As the Erowid FAQ puts it:

In this respect, GHB is probably comparable to alcohol: if you drink twice as much as you normally would, you probably wouldn't function very well.

The difference is that it takes time and effort to overdose on ethanol, but only a slip of the hand to overdose on GHB. So when using GHB it's extremely important to measure the dose precisely.

One should also be careful with redosing, realizing that there's still some GHB in your body from the previous dose (the elimination half-life is around 40 minutes, so effects can last a couple of hours).

Tolerance, dependence, and addiction: According to Erowid,

Many people enjoy the effects of GHB enough that they find themselves using it more frequently than they intended to or are comfortable with. Using GHB every weekend can turn into a few times a week or every night and can, for some people, turn into several times a day. People who find themselves using GHB daily or multiple times a day for periods of weeks or months often report that they have some difficulty ceasing use.

Reports of physiological GHB dependence all seem to occur in people taking it multiple times daily. They find they need to take higher and higher doses in order to feel good, and eventually just to feel normal, and that stopping leads to serious alcohol-like withdrawal symptoms. But lots of people report using GHB a few times per week over long periods of time, with no obvious consequences. From the Global Drug Survey:

The best way to avoid developing tolerance and dependence is to refrain from taking GHB for more than 2-3 days in a row. You can become dependent after as little as a few weeks of daily use.

All of this makes it sound pretty similar to alcohol, as far as I can tell. Don't use it daily --- ideally, limit it to social occasions --- and you'll probably be fine. Erowid seems to concur:

[GHB habituation and addiction] seem similar in level to the habituation and addiction that occur with heavy alcohol use, the main difference being that people generally feel better after coming down off of a single heavy use of GHB than they do with heavy alcohol hangovers, so this can lead to a perception that GHB has less negative side effects when used heavily.

Because excessive alcohol use usually 'feels bad' (hangovers, etc.), while GHB may continue to feel good even as frequency increases and dependence develops, it's up to your own conscience and willpower to be aware of your usage and not go overboard. Many people seem to manage this successfully, but it seems potentially dangerous for people who struggle with impulse control, are at a low point in life, and/or have ever had issues with addiction.

Interactions: GHB has significant synergy with alcohol and other GABA agonists (eg phenibut). Many horror stories involve passing out after drinking, because a single drink on GHB can have much more than its usual effect.

Toxicity: all the discussion I can find of GHB 'toxicity' focuses on the acute effects of overdose: respiratory depression, etc. Outside of these there don't seem to be significant concerns about long-term harm. The Erowid FAQsays:

For the thirty years prior to 1990, the scientific papers on GHB were unanimous in reporting numerous beneficial physiological effects and the absence of long-term negative effects. In 1964, Laborit listed "very low toxicity" as one of the "principle elements" of the compound's pharmacology. In a 1969 report on GHB's anesthetic uses, Vickers referred to GHB as "a truly nontoxic hypnotic" and repeatedly emphasized its "lack of toxicity." Vickers cited evidence that GHB demonstrates "no toxic effects on the liver and kidney." In 1972, Laborit described the body's metabolism of GHB and stressed "the absence of any need of detoxification by the organism." As recently as 1989, this scientific consensus on GHB's benign nature remained unchanged. Gallimberti's study from that year on its uses in treating alcohol withdrawal in humans notes that "GHB's action …seems to be without serious side effects." His almost off-hand reference to the "safety of GHB" shows how well-established this property of the nutrient had become. Then, on November 8th, 1990, the FDA banned the over-the-counter sale of GHB in the United States. In 1991, two scientists from the California Department of Health Services wrote a report on ten "poisonings" associated with GHB. The authors, Chin and Kreutzer, warned of GHB's "tremendous potential for abuse." They observed that "all interviewed patients reported a pleasurable sensation or a 'high'. Several of them…continued taking [GHB] because it made them 'feel good'." Apparently, the authors construed feeling good in and of itself as a potential threat to public health. Despite such dire language, the report acknowledged that "there are no documented reports of long-term [detrimental] effects. Nor is there any evidence for physiologic addiction."

Given all of this, how should one use GHB responsibly as an alcohol substitute? If I were to try it, I would enforce the following rules:

• Never use GHB more than three days per week, or two days in a row. These should be social contexts; solo use is permitted at most once per month (e.g., to test dosages for a new batch).
• Pre-measure all GHB doses into small vials of known capacity, so that it is physically impossible to overdose by consuming the contents of a single vial.
• Stick to 1-2 doses per day, never more than three.
• Always note the time of dosing and wait 90-120 minutes between doses.
• Never combine with alcohol.
• Be exceptionally careful if I've already taken phenibut that day - either avoid altogether or start at 0.1x dosage.

Probably these rules are stricter than absolutely necessary. Still, they should only be relaxed on the basis of long-term evidence from trustworthy sources (e.g., peer-reviewed publications), not just because I'm not personally noticing any negative effects.

References

• Wikipedia: https://en.wikipedia.org/wiki/Gamma-Hydroxybutyric_acid
• Erowid GHB Vault: FAQ