By Mark Gold, MD
Methamphetamine , a well-known psychostimulant drugs of abuse is in a resurgence in people using opioids and others. While many treatment options exist for patients with opioid use disorders, alcohol use disorders, and even tobacco smokers, there are far fewer options for people trying to stop using methamphetamines. No known medical treatments exist for overdose, dependence, craving, relapse, or to reverse all of the effects of methamphetamine binges and dependence. Experts studying substance use disorders recognize that their effects from misuse, especially the misuse of methamphetamine, can linger even after periods of abstinence.Patients treated for methamphetamine binges, or dependence, for example, often suffer from cognitive impairments, including psychosis. Some of the persistent problems may reflect underlying brain change or even damage. If overlooked, cognitive problems can limit the effectiveness of treatment. They can also create a dangerous hopelessness or relapse cycle. That’s one reason why it’s so important to understand how substances like methamphetamine may alter the brain’s structure.
How Long Do Methamphetamine Brain Changes Last?
Methamphetamine addiction is a growing epidemic worldwide, following on the heels of the opioid crisis. Chronic methamphetamine use has been shown to lead to neurotoxicity in both humans and animals Magnetic resonance imaging (MRI) studies in methamphetamine users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of abstinent methamphetamine users. Some features of the methamphetamine toxicity profile are puzzling as well as difficult to treat. In prior work, it’s been noted how psychosis can follow methamphetamine use and last into abstinence. Varying levels of methamphetamine use can induce psychosis, depending in part on an individual’s background, and it can develop quickly or after 20 years of use. This psychosis can be quite similar to Schizophrenia - in some cases, violent behaviors have been connected to methamphetamine psychosis as well. A study of Japanese prisoners found that a subgroup of methamphetamine users experienced chronic psychosis. Lingering cognitive problems may cause other health complications, difficulty thinking or concentrating at work, and increasingly risky behavior, in addition to higher relapse rates. Furthermore, later-in-life stress can also revive psychotic symptoms. More research on methamphetamine and cognitive problems can help treatment providers understand these hidden tripwires for patients.
One study, by Thanos et. al., looked at brain changes in rats after long-term methamphetamine use. Researchers split rats into 3 groups and gave them methamphetamine daily for 4 months. They dissolved methamphetamine in a saline solution and gave one rat group high methamphetamine doses, one rat group low methamphetamine doses, and the remaining rat group saline. Subsequent testing showed significant changes in the rats’ brains, stemming from higher doses. They also detected changes in brain glucose metabolism across different areas of the brain. These changes affect sleep cycles, face sensory processing, navigation, and memory. Researchers additionally found increases in striatal volume, referring to a part of the brain with a key role in decisions and reward management. These increases resemble the results of other research, an important part of the study. Cognitive problems in humans taking methamphetamine can exist before substance use. But Thanos et. al. observe that a combination of research on methamphetamine use and this part of the brain, involving humans, monkeys, and rats, all finds similar increases. Unfortunately, this combination indicates that some methamphetamine-induced problems in the brain are prolonged and significant. Thanos et. al. also start the rats’ substance use in adolescence. They point out that studies of human use in adolescence and adulthood find similar brain problems, adding to the likelihood of long-term damage. Thanos has continued this work with NIDA Director Volkow, looking at damage produced in the brain by methamphetamine. These most current results from their group, corroborate clinical experiences and reports of toxicity and encourage us to further examine the mechanisms behind MA-induced neurotoxicity.
Why Is This Important?
This kind of study is important because treatment and recovery providers need to understand the full spectrum of issues their patients face. Once the acute problems are resolved, many challenges may remain. Even in abstinence, brain problems after methamphetamine use may become substantial hurdles for patients in recovery. Psychological and neuropsychological testing may help the clinical team understand what has been lost and what might be done to help. Thanos et. al. also suggest that methamphetamine use may trigger a direct brain injury that we suggested was similar to a concussion or traumatic brain injury. Thanos suggests that methamphetamine targets the dopamine rich pleasure system, undermines it and the residual brain inflammation is both the proof and the cause of the post-drug changes to the health of our dopamine systems. Determining long-term methamphetamine brain changes can be even more useful for setting goals and interventions designed to help patients. Some of the strategies currently used to treat traumatic brain injuries may be helpful, as may use of exercise, dance, and transcranial magnetic stimulation. Post drug abstinence psychoses may not be as reversible by medications used for naturally-occurring psychoses. Many patients, for example, show subtle changes without clear signs of cognitive difficulties. Testing may reveal real problems. Others present with fears and anxiety or disordered thinking that may have there roots in changes to their brains. And untangling cause and effect can help us better understand when preexisting cognitive problems, and not substance use, are the main culprits. As with many substance use disorders, we have to remember that a holistic approach based on individual needs is the best way to help.
With methamphetamine this is even more important as medication assisted therapies do not exist. Time of abstinence, rehabilitation with healthy thinking, eating, sleeping, and diet are easier to prescribe or advise than find. Time of abstinence is of the essence as it appears that methamphetamine induces a drug use disorder with binges, relapses and cravings but also with loss of brain function and evidence of something that looks like a traumatic brain injury. Treating it like a neurological injury in addition to traditional addiction treatment, may be an idea worth looking at too.
Chan B, Freeman M, Kondo K, Ayers C, Montgomery J, Paynter R, Kansagara D. (2019) Pharmacotherapy for Methamphetamine/Amphetamine Use Disorder - A Systematic Review and Meta-analysis. Addiction.
Thanos PK, Kim R, Delis F, Ananth M, Chachati G, Rocco MJ, Masad I, Muniz JA, Grant SC, Gold MS, Cadet JL, Volkow ND. (2017) Chronic Methamphetamine Effects on Brain Structure and Function in Rats. PLoS One.
Gold MS, Kobeissy FH, Wang KK, Merlo LJ, Bruijnzeel AW, Krasnova IN, Cadet JL. (2009) Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates. Biol Psychiatry.
Cadet, Jean Lud, Gold, Mark. (November, 2017) Evidence -Based Review. Methamphetamine-induced psychosis: Who says all drug use is reversible? Current Psychiatry. Retrieved from https://www.mdedge.com/psychiatry/article/150344/addiction-medicine/methamphetamine-induced-psychosis-who-says-all-drug-use
Akiyama K, Saito A, Shimoda K. (2011). Chronic methamphetamine psychosis after long-term abstinence in Japanese incarcerated patients. Am J Addict
Thanos PK, Kim R, Delis F, Ananth M, Chachati G, Rocco MJ, Masad I, Muniz JA, Grant SC, Gold MS, Cadet JL, Volkow ND. (2017). Chronic Methamphetamine Effects on Brain Structure and Function in Rats. PLoS One.
Gold MS, Kobeissy FH, Wang KK, Merlo LJ, Bruijnzeel AW, Krasnova IN, Cadet JL. Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates. Biol Psychiatry.
Thanos PK, Kim R, Delis F, Ananth M, Chachati G, Rocco MJ, et al. (2016) Chronic Methamphetamine Effects on Brain Structure and Function in Rats. PLoS ONE
Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.