How is Drug Addiction Defined?
Drug addiction can be defined as the inability for an individual to control or regulate compulsive seeking out and use of drugs. Behavioral changes in response to habitual, long-term drug use, including dependence, withdrawal, and relapse, can largely be attributed to physiological implications of drug use. In the literature article, “Cellular basis of memory for addiction,” Dr. Eric J. Nestler explores alterations in cellular physiology within the brain in response to drug abuse. Alterations of various molecular aspects, such as transcription factors, epigenetic mechanisms, synaptic plasticity, and whole cell plasticity, all contribute to the intense cognitive and behavioral consequences of drug abuse.
Sex Differences in Response to Drugs
There is an unexpected relationship between men and women in response to drugs use and addiction, as women are more likely to experience many of the behavioral responses to drugs at a quicker rate than men, consequently promoting increased likelihood of addiction to drugs of abuse. Research and experimentation using animal models have shown that female rodents are more likely than male rodents to:
- increase administration of drugs of abuse more quickly (i.e. tolerance)
- have greater motivation to consume the drugs of abuse in the first place, along with higher initial doses of the drugs
- experience greater rewarding effects of drugs
- experience more intense negative withdrawal symptoms
- begin using drugs again after a period of abstinence (i.e. relapse)
Why is there a Difference Between Males and Females in the Response to Drugs and Addiction?
There is a correlation between fluctuations of the ovarian hormones of estrogen and progesterone and the greater likelihood that women over men will become addicted to a drug, become addicted at a faster rate, and will be more prone to relapse. Research has shown that fluctuations of these two hormones throughout biological events including the menstrual cycle, menopause, and the postpartum period undoubtedly modulate the effects of drug abuse and addiction in those who menstruate.
Estrogen and Drug Addiction
In animal studies, female rates consume higher doses of cocaine when estrogen levels are high and lower doses of cocaine when estrogen levels are low. Additionally, estrogen increases and reinforces both the rewarding properties of opioids and heroin. These characteristics can be explained through a signal transduction event in which estrogen leads to the phosphorylation and therefore activation of the protein CREB. CREB is a transcription factor that induces transcription of genes that reduce sensitivity to the rewarding effects of drugs of abuse (i.e. establishing tolerance) and perpetuate the negative withdrawal symptoms that accompany drug abuse, thereby promoting dependence on the drug. These effects of CREB also make the drug user more prone to relapse as a result of the greater rewarding effects of using the drug and the intense negative effects of withdrawal from the drug.
Progesterone and Drug Addiction
Maintaining the opposite effect of estrogen, higher levels of progesterone actually have a protective effect in reducing the intensity of drug cravings and the probability of relapse. An example of how progesterone can reduce drug addiction behaviors can be clearly seen in nicotine addiction. Within nicotine addiction, the receptor that binds nicotine in the brain, called the nicotinic acetylcholine receptor (nAChR), plays a central role in producing the reinforcing effects of nicotine. Progesterone blocks these receptors, preventing these reinforcing effects to take place and perpetuate addiction. When evaluating the effects of progesterone, it is important to observe the luteal phase of the menstrual cycle that occurs after ovulation, in which the follicle that had once stored the egg develops into a structure called the corpus luteum that secretes progesterone. The end of this period of time poses a high risk for drug cravings, intense negative withdrawal symptoms, and relapse due to a sharp reduction of progesterone during this phase. As a result, exogenous progesterone can be utilized as a supplemental treatment that has been found to be successful in undermining many behavioral consequences to drug addiction.
Menstrual Cycle Tracking as a part of Treatment Strategies
As a result of these fluctuations in ovarian hormones throughout the course of the month and their respective contributions to drug addiction, it would likely be beneficial for those struggling with drug abuse to look into tracking their menstrual cycle as a component of therapy. When an individual approaches periods of time throughout menstruation, menopause, or pregnancy in which estrogen levels are high and/or progesterone levels are low, it is important that they have the knowledge that they will be at greater risk for drug cravings and relapse during those times. Consequently, those struggling with addiction may be more diligent and avoidant of drug-associated stimuli during these periods of ovarian hormone fluctuations. Further research regarding addiction and these hormones should ultimately be pursued in order to better aid those combating drug addiction.
Abstract/Featured Image created by S. Wiger
