Dr. Thomas Kosten gave 2 presentations on Stimulant Misuse at the recent Addiction Medicine 2020 virtual conference: Epidemiology, Neurobiology, Pharmacology and Clinical Impact on Treatment of Stimulant Disorder and Clinical Response: Behavioral and Medication Options.

Despite the significant amount of time was allotted for live Q&A, there were additional questions that we asked Dr. Kosten to answer afterward. The volume of stimulant-related questions speaks to the immense challenges that are currently posed by misuse of stimulants, particularly cocaine and methamphetamine.

Q: Why doesn’t Ritalin use cause these same problems – or does it show up as they children become adults?

  • A: The dose of Ritalin is much smaller than abused doses of cocaine or amphetamine or methylphenidate (Ritalin) and the underlying brain of an ADHD child has some dopamine abnormalities that are normalized by the low or therapeutic doses of this medication.  Thus, no brain damage is induced in children or adults.  

Q: This sounds rather hopeless and irreversible. How does one manage the combination of fentanyl and cocaine?

  • A: We have no FDA approved medications for cocaine, but I have used disulfiram 250 mg daily and doxazosin 8 mg daily as two potential medications.  Fentanyl abuse has some potential for partial blockade using higher doses of buprenorphine such as 24 mg daily.

Q: Are similar changes seen with ADHD patients with long term treatment?

  • A: See answer to question #1, no brain damage is produced.

Q: Are the destruction of dopamine receptors irretrievable or is there plasticity to support the hope that abstinence could result in some restoration?

  • A: The data from longer term follow-up is that DA receptors and their associated cells can grow back over several years, but overall the DA system deteriorates as people age and so massive destruction of 50-60% at a young age, leaves little reserve for the otherwise self-limited “life span” of these neurons.  Parkinson’s disease develops when more than about 70% of DA neurons become damaged and cannot function.

Q: Are these changes seen with therapeutic psychostimulant treatment?

  • A: No,See question #1.

Q: Can we expect these long term outcomes for those with ADHD?

  • A:  No, see question #1.

Q: Is ADHD being over diagnosed and treatment?

  • A: Yes, it appears over-diagnosed, particularly in adults and college students, and using stimulants for those without ADHD is not helpful.

Q: Should long acting ADHD treatment be used?

  • A: Long acting rather than short acting stimulants should be used for ADHD treatment, and the duration of treatment generally seems to have limited efficacy beyond age 18 in children who have this disorder. They become “normalized” by stimulant treatment during the prior 10-12 years starting at 6-8 years old.

Q: I have seen long lasting delusional disorders following long term use of meth. Do you see this and does this get better over time?

  • A: This is mostly reported from Japan and does not seem to respond to our typical antipsychotic agents and leads to a deficit type of delusional state with a general intellectual deterioration over time rather than improvement, if that improvement does not occur within a couple of months of stimulant abstinence.

Q: Do people with ADHD and Stimulant Use Disorder reduce their stimulant use if they are treated for ADHD?

  • A: Sometimes and there are multiple case reports about that. Recently Fran Levin published a study using long acting, slow release amphetamine at 60 mg daily along with topiramate and showed reduction in stimulant abuse among those who had prior ADHD.

Q: Is Naltrexone a good adjunct in Methamphetamine abusers?

  • A: The clinical trials are mixed. It looked very effective in two studies from Iceland, but could not be replicated in the USA. There may be a pharmaco-genetic factor that is important, since Iceland has a relatively in-bred population that would tend to express recessive genetic variants that would be masked in a more heterogeneous population like the USA. We do not know what that genetic variant is however.

Q: Is there any clinical significance to the production of coca ethylene from co-administration of alcohol and cocaine?

  • A: Yes, this compound is more potent and longer lasting than cocaine, so it can produce more toxicity and particularly can produce more paranoia and anxiety in some abusers, although alcohol+cocaine is a very popular combination, as you know.

Q: What about Vraylar for stimulant cravings?

  • A: I do not know of any studies examining this antipsychotic agent, but most of them make cravings and use worse.

Q: Could you comment on the use of topiramate with cocaine-use disorder? We’ve used it among our MAT patients with cocaine use, with some success.

  • A: Yes, Kyle Kampman at U Penn and Bankole Johnson at a new company have used  it with some success for cocaine use. Dropout during the induction period can be a problem and those using alcohol + cocaine seem the best candidates for it.

Q: Can you comment on Clostridial blocking of DBH (by 4-cresor &/or HPHPA) contributing to Autism spectrum behavior by affecting dopamine/NE ratio?

  • A: I don’t know about this particular association, but DBH blocking with markedly reduce NE production and increase the DA/NE ratio substantially. This enzyme and its functional genetic polymorphism was studied for over 20 years as a potential contributor to schizophrenia. Joe Cubells at Emory could probably be helpful for that question.

Q: Mirtazapine for meth?

  • A: A very interesting study from San Francisco came out last year for using it in gay men with success. I have not seen a replication of that study in women or outside of San Francisco.

Q: Do you have an opinion on the ReSet App?

  • A: It is a sound idea based on contingency management principles, and can be effective with patients who can afford to fill the “prescription” for it.  No federal insurance policy will cover it, and most commercial policies do not cover it, but it could  be effective.

Q: You’ve certainly presented an argument for why CBT may not be effective – do you have data to show that (in clinical trials) CBT isn’t effective?

  • A: The best data with CBT for stimulants has been done by Kathy Carroll at Yale.  She found some very interesting delayed effects of CBT, in which patients at 6 month and 12 month follow-up after completing a 3 month course of CBT had much better outcomes than those who did not get CBT.  She called it a “sleeper effect” in maintaining abstinence, and may reflect that CBT best efficacy can occur after a few months of abstinence and brain recovery and normalization. I use a computer based version of CBT, called CBT4CBT and combine it with medications such as disulfiram or doxazosin.  The patients seem to get quite engaged with the virtual reality type of CBT, which they can engage at any time, and it is always awake, unlike human therapists, who need to sleep at night.

Q: For the antagonists, do any of them reduce non-neurologic effects of stimulant use (e.g. cardiovascular)?

  • A: The only antagonists for stimulants that I think could be effective are the vaccine or enzyme type of blockers.  Direct DA receptor blockers have repeatedly failed in clinical trials.  The vaccines block all of the stimulant effects including cardiovascular by trapping the inactive stimulant in the blood stream until it is metabolized or excreted.

Q: If started on agonist treatment, how long do patients stay on those meds?

  • A: I recommend a minimum of 2 years. Most remain for about 6 months and then declare themselves cured. Some of my patients have been taking agents like modafinil for 3-4 years, and I think that the agonists for stimulants like long acting slow release amphetamine will have the longest duration of adherence. Like methadone or buprenorphine patients may take those agonists for many years, but those studies will likely happen in Australia or Great Britain, since the USA government is opposed to that type of therapy.

 

We’ll answer more questions from the virtual Addiction Medicine Conference in upcoming newsletters.

Be on the lookout!