Salon recently posted a history of cocaine. Has PHARMA changed at all?
For serious cocaine consumers, other products were also available in the late nineteenth century. Large drug companies such as Parke-Davis in Detroit also got into the cocaine game. They developed processes for the mass production of easily crystallizable and soluble salts like hydrochloride, which could be accurately measured and dispensed. Finely powdered “lines” of cocaine could easily be “snorted” through a cut straw or rolled up banknote and would enter the well-vascularized mucous membranes in the nose and move from there into the blood and then the brain relatively quickly. Naturally, the most efficient way of taking cocaine, just like morphine, was to inject it intravenously. To satisfy this portion of the cocaine market, drug companies like Parke-Davis also came up with drug-taking paraphernalia such as nifty little boxes that contained syringes, needles, and supplies of cocaine all packaged together as a fashion accessory for the smart set. According to Parke-Davis’ own ads, cocaine “could make the coward brave, the silent eloquent, and render the sufferer insensitive to pain.” As we have seen with other powerful and potentially dangerous drugs, the end of the nineteenth and the beginning of the twentieth century was a time when these things were generally available and not illegal. In fact, cocaine could be purchased over the counter in the United States until 1916.
“Using an intent-to-treat analysis, the researchers found that topiramate was more efficacious than placebo at increasing the participants’ weekly proportion of cocaine nonuse days and in increasing the likelihood that participants would have cocaine-free weeks,” the university said Friday in a statement.
Similarly, Johnson’s team found a significant association between topiramate and both a decrease in craving for the drug and an improvement in the subjects’ overall level of functioning in comparison to a placebo.
Here are a few things you should know.
What does “more efficacious than placebo” mean? It means that the number of days subjects did not use cocaine increased to 13.3% or 8.9%. (Depending on how you calculate it.) So, subjects still used cocaine 86.7% or 91.1% of days.
The lead researcher left his last post after losing a whistleblower lawsuit. One of his projects had been accused improperly charging the federal government for time spent on a study. He also attacked the character of the whistleblower.
“The study performed cannot determine whether Oreos are as addictive as cocaine,” said Edythe London, a researcher at the University of California, Los Angeles, who uses brain imaging to study the neural basis of drug cravings. “That question is best addressed in a comparison of how hard a rat will work for Oreos versus cocaine — how many times a rat will press a lever to get one or the other.”
The students also measured the expression of a protein called c-Fos, which indicates brain cell activity, in the nucleus accumbens of rats exposed to Oreos or cocaine. This brain region is important for pleasure and positive reinforcement and is involved in addiction because of the pleasurable feelings brought on by drugs.
The rats’ nucleus accumbens activated more strongly with the stimulus of Oreos than the stimulus of cocaine, but those findings don’t prove anything about the addictive potential of the cookies, either, London told LiveScience.
The study is “consistent with the fact that Oreos produce pleasure — but we knew that,” London said.
“When they were given an alternative to crack, they made rational economic decisions.”
When methamphetamine replaced crack as the great drug scourge in the United States, Dr. Hart brought meth addicts into his laboratory for similar experiments — and the results showed similarly rational decisions.
“If you’re living in a poor neighborhood deprived of options, there’s a certain rationality to keep taking a drug that will give you some temporary pleasure,”
I was thinking about it a little more and several people have spoken with me about it.
I have two thoughts that I’d add to yesterday’s post.
Dirk Hansen reports the good news about “crack babies”:
In a paper authored by Hurt, Laura M Betancourt, and others, the investigators write: “It is now well established that gestational cocaine exposure has not produced the profound deficits anticipated in the 1980s and 1990s, with children described variably as joyless, microcephalic, or unmanageable.” The authors do not rule out “subtle deficits,” but do not find evidence for them in functional outcomes like school or transition to adulthood.
And, the bad news:
As FitzGerald writes: “The years of tracking kids have led Hurt to a conclusion she didn’t see coming. ‘Poverty is a more powerful influence on the outcome of inner-city children than gestational exposure to cocaine,'” Hurt said.
He asks, “How did this urban legend get started?”
In the 1980s, during the Reagan-Bush years, Americans were confronted with yet another drug “epidemic.” The resulting media fixation on crack provided a fascinating look at what has been called “drug education abuse.” This new drug war took off in earnest after Congress and the media discovered that an inexpensive, smokable form of cocaine was appearing in prodigious quantities in some of America’s larger cities. Crack was a refinement to freebasing, and a drug dealer’s dream. The “rush” from smoking crack was more potent, but even more transient, than the short-lived high from nasal ingestion.
Another study supports the effects of twelve step participation over 24 months. (I know the abstract says “self help”, but the pay-walled article makes it clear that they were looking at twelve step participation.)
The goal was to identify factors that predicted sustained cocaine abstinence and transitions from cocaine use to abstinence over 24 months. Data from baseline assessments and multiple follow-ups were obtained from three studies of continuing care for patients in intensive outpatient programs (IOPs). In the combined sample, remaining cocaine abstinent and transitioning into abstinence at the next follow-up were predicted by older age, less education, and less cocaine and alcohol use at baseline, and by higher self-efficacy, commitment to abstinence, better social support, lower depression, and lower scores on other problem severity measures assessed during the follow-up. In addition, higher self-help participation, self-help beliefs, readiness to change, and coping assessed during the follow-up predicted transitions from cocaine use to abstinence. These results were stable over 24 months. Commitment to abstinence, self-help behaviors and beliefs, and self-efficacy contributed independently to the prediction of cocaine use transitions. Implications for treatment are discussed.
It’s worth noting that some of these factors predicting abstinence are enhanced by twelve step participation:
These models represented fairly stringent tests of the predictive power of the time varying variables, as they controlled for both baseline (i.e., early treatment) cocaine use and cocaine use status at the time the predictor variables were assessed. In analyses that included multiple time-varying predictors and baseline cocaine use, the variables that contributed independently to the prediction of transitions in cocaine use states were self-efficacy, self-help participation (for those who were currently using cocaine), commitment to abstinence, and self-help beliefs. Three of these four variables assessed self-help group related factors, which highlights the important role that self-help involvement and beliefs play in sustained recoveries in this population.
This study did not find a significant main effect of modafinil on the rate or duration of cocaine use among cocaine-dependent patients.
Now they decide to polish the turd:
Although these results are disappointing, we did find that modafinil-treated patients had nonsignificantly higher odds of attaining abstinence across all of the study time points, and those treated with 400 mg/day had significantly greater odds of attaining abstinence (p = .04) at the end of their 8-week medication trial (Visit 24). There was also a significant difference (p = .02) in the OR for abstinence at the final follow-up visit, suggesting the possibility that modafinil facilitated delayed clinical improvement that was not captured by our 8-week study design.
It is important to note that all of the patients in this study tested positive for cocaine at baseline. It is well established that patients who test positive for cocaine at study start have extremely poor clinical outcomes when compared with those who are able to produce a cocaine-negative urine sample ( [Ahmadi et al., 2009],[Kampman et al., 2001], [Patkar et al., 2002] and [Poling et al., 2007]). The reason for this finding is unclear, but it probably stems from greater addiction severity, less motivation for recovery, or both of these clinical features.
There will be evidence, dammit!
Despite our negative study, we believe it is premature to dismiss modafinil as a potential treatment for cocaine dependence.
Measurements Subjects completed nine experimental sessions in which they were pre-treated with 0, 100 or 200 mg oral immediate release bupropion. Ninety minutes later they sampled an intranasal cocaine dose [4 (placebo), 15 or 45 mg] and made six choices between that dose and an alternative reinforcer (US$0.25), available on independent, concurrent progressive ratio schedules. Subjects also completed a battery of subject-rated, performance and physiological measures following the sample doses of cocaine.
Findings After 0 mg bupropion, the high dose of cocaine (45 mg) was chosen five of six times on average compared to 2.25 of six choices for placebo cocaine (4 mg) (P < 0.05). Active bupropion reduced choice of 45 mg cocaine to 3.13 (100 mg) or 4.00 (200 mg) out of six drug choices on average. Bupropion also consistently enhanced positive subject-rated effects of cocaine (e.g. good effects; willing to take again) while having no effects of its own.
Conclusions The atypical antidepressant, bupropion, acutely appears to reduce preference for intranasal cocaine versus a small amount of money but to increase reported positive experiences of the drug.
A recent study gets into some of the nitty gritty of substance use disorders and interpersonal violence (IPV):
Alcohol use disorders and cocaine use disorders were most strongly associated with IPV perpetration,
while cannabis use disorders and opioid use disorders were most strongly associated with IPV victimization.
A diagnosis of both an alcohol use disorder and cannabis use disorder decreased the likelihood of IPV perpetration compared to each individual substance use disorder.
A diagnosis of both an alcohol use disorder and cocaine use disorder increased likelihood of reporting IPV perpetration compared with alcohol use disorders alone but decreased likelihood of perpetration compared with a cocaine use disorder diagnosis alone.