Gamma Hydroxybutyrate (GHB) is a potent sedative and widely abused drug that is associated with myriad instances of date rape. The drug's actions in the central nervous system are not clearly understood but they are similar to the effects of alcohol with an addictive potential that may be much worse. GHB addiction and dependency are often difficult to identify. Treatment methods for GHB-dependent patients are unsettled. GHB's impact as a drug of abuse are amplified by abuse of precursors gamma butyl-lactone (GBL) and 1,4 butanediol (BD).

 

Jazz Pharmaceuticals manufactures the drug Xyrem, a chemical knockoff of GHB. The drug is currently approved by the FDA for treatment of cataplexy associated with narcolepsy and for excessive daytime sleeping. In recent years, Jazz Pharmaceuticals and a number of physicians have pushed for use of Xyrem to treat fibromyalgia. The disease has proven to be difficult to treat. Physicians have been relying on prescription antidepressants and membrane stabilizing drugs for their patients. The disease afflicts women disproportionately. Empirically in off-label use of Xyrem, there was some evidence that the drug could be helpful to fibromyalgia patients.

 

A DFA advisory panel voted 20-2 against approval of the drug. It was clear that the panelists were sensitive to Xyrem and GHB's abuse potential. Xyrem is sodium oxybate, a salt of GHB. Xyrem has been diverted in much the same way as other prescription drugs. On the street, the drug has widespread potential for abuse. Aside from the drug's potential for abuse, panelists were taken aback by the drug's odd dosing mechanism. Like GHB, Xyrem has a very short half-life. For the drug to be clinically effective patients have to take frequent doses of the drug; some patients are instructed to wake up in the middle of the night and mix a dose and then try and get back to sleep. Patient testimonials also point to the very rapid onset of the drug's effects. In some instances, the drug's effects are causing some patients to pass out within a minute of administration. 

 

So for the moment, Xyrem has suffered a defeat. But company executives vow to continue meeting with the FDA in an effort to get the drug approved in the future.

The mystery drug for this edition of the DARS Newsletter is a substance that is the final representative of a class of abused substances that was a national scourge from the end of World War II until the end of the Vietnam War. In its current manifestation, the drug can be found as a stand-alone medication or it can be combined with a narcotic, such as codeine to boost its efficacy. This drug can not be found or purchased over the counter; it is regulated under the terms and conditions of federal Schedule III. Interestingly, the drug is more commonly prescribed to women than it is to men. This drug can be addictive and can lead to the development of a painfully strong drug dependency. Withdrawal from the drug can lead to seizures and a host of unpleasant effects.

 

This drug is a descendant of a large family of substances that were the backdrop to the surge in drug use seen in the 1960s. Hippies and counter-culture warriors hyped the value of this class of drugs in the pursuit of Timothy Leary's mantra, "Turn on, tune in, drop out." This month's drug is not a hallucinogenic. Law enforcement and healthcare officials were acutely aware of the risks associated with its use. During the Nixon Administration, the Drug Enforcement Administration (DEA) came into existence in part as a governmental response to the non-medical use of this class of drugs. The drugs of this class that preceded this month's mystery drug were nearly all classified in federal Schedule II, the most highly regulated designation that a prescribed medication is assigned. Nearly all of those medications that dominated drug-using scenes of the 60s and 70s have now left the market.  

 

On the street, the drugs of this class were mostly identified by the bright colors of the capsules that contained them. "Reds," "yellows" and "rainbows" were the street names that attached to these drugs. Police television shows of the era frequently ran episodes of drug investigations where some miscreant who was trying to lure unsuspecting teenagers was arrested in possession of large plastic bags that were full of red and yellow capsules. Sergeant Joe Friday of the 1960s television series "Dragnet" frequently opined on the insidious nature of these drugs and the dealers who scurried around like cockroaches moving from one dark place to another. Users of these drugs were portrayed as helplessly addicted, and frankly, many of them were. In those days, the drugs were routinely administered through intravenous injection. The injection sites left considerable scarring and bruising. One of the most reliable indicators of use was "tracks" on the hands and in the antecubital space of the forearm. Movie stars and entertainers dabbled in the use of these drugs, some use resulting in death. Marilynn Monroe's death can be blamed on the dangers of this class of drugs.

 

A descendant of earlier and more dangerous versions, this month's drug is a prescription medicine and is of lesser potency than the other drugs and compounds in the larger family. As a controlled substance, physicians must be careful with how the drug is applied to a medical problem. This drug is a central nervous system depressant. For readers who are DAR or DRE trained, signs and symptoms of someone "high" on the drug will be located in the "depressant" category.  At low to moderate doses of 50 milligrams, the symptoms will be subtle. At higher doses of 100 milligrams or more, classic presentations of nystagmus and non-convergence will be seen. Droopy eyelids (ptosis) may be present, pupillary reaction to light will be slow. At the higher doses, a user may appear to have been drinking, but without an odor of alcohol. Slurred speech, degraded balance, and loss of coordination are all possible at higher doses. Like other members of its class, this month's drug is capable of causing an alcohol-like physical dependency. Withdrawal intensity varies based on the daily amount of drug that is consumed. For people using more than 300 milligrams a day, the withdrawals may require supervised detoxification. Ironically, this class of drugs was frequently prescribed in the early and mid-20^th century to alcoholics who were experiencing more violent withdrawals. Ultimately, this class of drugs was replaced by benzodiazepines, the family of substances represented by drugs such as Valium, Xanax, and Ativan.

 

This month's drug is approved by the FDA for use in the treatment of migraine headaches. The drug is considered a second line treatment for patients who do not respond well to the tryptamine-based drugs (Imitrex, Maxalt, Zomig). The triptans (serotonin receptor agonists) are the first line of defense to abort migraine and cluster headaches. In instances where headaches do not respond well to the utilization of the triptans, this month's mystery drug is a reliable alternative. In recent years, the drug has also been used in the practice of pain management. In particular, the drug is prescribed for stubborn cases of fibromyalgia. Women are disproportionately felled by fibromyalgia, which is why the drug is more commonly used by women than by men. Physicians know that this drug has potential addiction liabilities; most will avoid prescribing this drug until other pharmaceutical options have failed.

 

This month's drug does experience diversion to sources that then deal it on the street. A 50 mg tablet can command $5 to $10 on the streets of Los Angeles. Mixed with alcohol, there is a synergistic potency that occurs with this drug. The drug has been periodically partnered with stimulant drugs, such as cocaine and methamphetamine. In that role, the drug helps create a "speedball" effect where diametrically opposed forces kick the central nervous system into gear going into opposite physiological directions. For some drug users, the "speedball" can be the ultimate thrill.  In addition to street use, the drug is often found at adolescent cabinet parties. Kids pour out all the drugs they have taken from the family medicine cabinet and let friends pick and choose what they want to take to get high. In some east coast reports, users have resorted to smoking this drug by mixing it in with marijuana in a hand-rolled joint.

 

The drug seems to be more popular with patients when combined with codeine. In its most common iteration, the drug is mixed with acetaminophen and caffeine. The caffeine mix is interesting. Caffeine certainly tends to offset the sleepiness that can attach with the use of the drug, but more importantly is its value as a vasoconstrictor and the role it plays in reversing migraine actions on blood vessels in the brain.

 

Fiorinal and Fioricet are two of the more common product names for this drug. Its formal chemical name is 5-allyl-5-isobutylbarbituric acid, the latter part of this designation is a giveaway to its identity.

 

This month's drug is Butalbital.

 

Kratom is extracted from the leaf of a tree that grows widely and wildly in Southeast Asia. Concentrated in the Kratom leaf is an alkaloid known as mitragynine. This alkaloid is one of probably many that are concentrated in the plant. The active chemical of mitragynine has some similarities to the tryptamine family of abused drugs here in the United States. That class of drugs has experienced consistent popularity as alternatives to mainstream stimulating hallucinogens. Kratom seems to produce some of the same paradoxical effects as the tryptamines but it does so less powerfully and for shorter lengths of time. The unusual effects of this drug flow from its action as an agonist of the mu opiate receptor. The drug produces sedating effects as a result of this action, but it does so while increasing a users sense of wakefulness, especially at lower doses. In Southeast Asia, it's common to find laborers walking around with a wad of Kratom wedged in their mouth. These people chew the leaf much like coca leaves are chewed and crushed by natives in Bolivia, Peru and Ecuador. The drug is purported to have properties that can cause the release of the neurotransmitter serotonin in the central nervous system too. This sort of effect acts as a biochemical cushion against a crash from its mu opiate receptor activity. Some users have related their tendency to use Kratom to lessen the harsh symptoms caused by withdrawal from other opiate preparations.

 

Kratom doesn't appear to grow here in the United States. Kratom products abound on the Internet, most appear to be extracts of the leaf. There are some sites that cater with actual Kratom leaf. But someone who is taking Kratom in one of its forms is likely to exhibit symptoms of someone under the influence of a low dose opiate. Because it is a mu receptor agonist, evaluators should expect to find constricted pupils (miosis), a sluggish to no reaction of the pupil to light, slowed Romberg clock and a slow deliberate gait and pattern of speech. The span of psychogenic effects for Kratom is 2-3 hours. Kratom use can become chronic for those users who are predisposed to addiction. Kratom can be addicting and it can cause opiate like withdrawals for those users who suddenly stop taking the drug following chronic abuse. It does not appear that Kratom has experienced much diversion and trafficking into adolescent using groups. The drug's rather limited availability and stiff price tag (for the good stuff) seem to have acted as a barrier to cross over into teenage drug using circles. Some off-key health food stores carry Kratom leaf products on their shelves, but expect most products to come from Internet sites that are headquartered overseas in Thailand. In Thailand, the drug is controlled substance and is popularly abused.

 

Despite the frequent calls the Hotline receives about this drug, it does not seem to be much of a public safety threat on our streets. The drug seems to be more a curiosity for those users who are attracted to the hallucinogens and opiates. Although most forensic laboratories can screen for the principal alkaloids in Kratom, it can be costly. If you live or work in a community where Kratom has a foothold, contact your laboratory sales representative and discuss the options for testing. DAR users can contact the DAR Hotline for situations where Kratom abuse is suspected. Kratom will likely produce both opiate and hallucinogen groups of symptoms.