Addiction-brain effects – Tolerance, sensitization, and withdrawal

If you’ve been with us for any length of time, you’ve already read about the addiction-brain effects for specific drugs. I think it’s important to understand some of the more general changes that occur in the addicted brain regardless of the specific drugs used.

One of the most common effects of long term drug use is something called tolerance, or the reduced effect of a drug dose. A lot of people know about this one, especially if they’re users and have found themselves needing to use more and more to get the same effect. However, while this is the most known, it is not the only change in the body, or brain’s, response to drugs with repeated use. The other effect, known as sensitization, is characterized by the exact opposite reaction – an increase in the response to the drug.

Tolerance & Withdrawal in the addicted brain

toleranceThe exact mechanism by which tolerance occurs is different for each drug, but the overall concept is the same. With repeated drug administrations, the body adjusts its internal processes in an attempt to return to its initial level of functioning. Drug use normally causes greater quantities of neurotransmitters like dopamine, serotonin, the opioids, and adrenaline to be present in the drug user’s synapses (see here for a review). The body counters this by reducing its own release of these chemicals, reducing the numbers of receptors that can be activated by the neurotransmitters, and increasing functions known as “opponent processes” that are meant to counter their activity.

The interesting thing about tolerance is that by reducing the level of these important neurotransmitters, addicts are left with another, possibly more important effect, which is the loss of the addicted brain’s ability to respond to any reward, including natural ones like food, sex, enjoying a good football game, or anything else. Essentially, this sort of cross-tolerance leaves the addict less able to respond to rewards in general.

The reduced response to drugs, and the corresponding changes in the body and brain’s own functioning, have long been thought to be a major cause of addiction. The withdrawal that results once drug taking stops is closely linked to the development of tolerance. Still, we now know that tolerance and withdrawal are not necessary, and certainly not sufficient for the development of addiction. Nevertheless, they are referred to as the physical dependence portion of addiction and are often are part of the overall picture.

Sensitization

Sensitization is the term used for an increased response to the same dose of a drug. That might sound a little oxymoronic after the tolerance discussion we just had, but bare with me.

Tolerance commonly develops when drug use is constant, or ongoing. It’s an aspect of chronic, long-term, use. On the other hand, sensitization is likely to occur when a user engages in intermittent, binge-like, drug use happening either once daily, or with even greater spacing (as in once every few days) and in large quantities. When you combine chronic use with binge behavior, you can actually get both responses.

Sensitization to drugs has been shown for physiological responses like heart-rate, blood pressure, and movement in animals and humans. More importantly, sensitization plays a part in increasing the motivation for drug use. Just like sensitization increases the physical response to drugs, there is a corresponding increased response in the addicted brain in areas important for motivation (like the NAc and VTA for instance). If an addict responds more to their drug of choice after repeated use, it should come as no surprise that sensitization has also been hypothesized to play an important role in the addiction process.

Drugs cause brain changes that drive addiction

opponent processesWhen both tolerance and sensitization develop in someone who has been using drugs, they’re left with a reward system that is less responsive to rewards in general while being more responsive to the drugs they’ve been binging on and to cues (or triggers) that are associated with those drugs. If that sounds like a recipe for disaster, it is. If you’re an addict yourself, you don’t have to imagine this, you’ve lived it – A state where nothing seems rewarding without being high.

The problem is that both tolerance and sensitization are examples of changes in response to drugs that are completely outside of the control of the user. There’s no doubt that the average drug user doesn’t think about, or even recognize, that as they continue to use drugs, their body adjusts in multiple ways that can make it that much harder for them to stop use at a later point. It should be clear that this is not an issue for everyone – both tolerance and sensitization require repeated administration of drugs that are pretty close together. But they don’t require hundreds of uses, a few days with continuous, or intermittent use, are often enough to bring about these changes in the addicted brain.

We often hear that even the first hit of a drug can cause someone to be addicted. While there’s little doubt that even a single drug administration can change brain response in important ways, I can say with absolute certainty that using a drug repeatedly cause long-lasting changes in the brain chemistry that make future drug use more likely.

Addiction-brain effects: Sex addiction, neurotransmitters, and being love addicted

***A disclaimer: Sex addiction is a relatively new concept in science. I haven’t been able to find much research on the subject, so much of what is being said here is my interpretation of the current literature on sexual responsivity in humans.***

sexI’ve already mentioned that scientists are beginning to consider behavioral addictions (like gambling and sex) as being similar to drug addiction. We’ve also covered sex addiction on the site quite a few times.

Since we’d covered the addiction-brain effects of some of the major drugs’ (see here for opiates, crystal meth, and cocaine), I thought it’s time to write about the possible science behind sex addiction.

The sexual activity cycle

Scientists have divided human sexual interaction into 4 stages:

  1. Desire – Represents a person’s current level of interest in sex. It is characterized by sexual fantasies and a desire to have sex.
  2. Arousal – Includes a subjective sense of sexual pleasure accompanied by a physiological response in the form of genital vasocongestion, leading to penile erection in men and vulva/clitoral engorgement and vaginal lubrication in women.
  3. Orgasm – Involves both central processes in the brain and extensive peripheral effects. Orgasm is experienced by the peaking of sexual pleasure, release of sexual tension, rhythmic contraction of the perineal muscles and pelvic reproductive organs, and cardiovascular and respiratory changes.
  4. Resolution – The final stage of the normal sexual response cycle. There is a sense of release of tension, well being, and return of the body to its resting state.

After sexSex addicts don’t seem to have a problem with stage 3, and resolution is more like the end of sexual behavior. So we will focus the rest of our attention on the other stages 1 and 2.

Sex and neurotransmitters

While sex doesn’t involve the ingestion of substances, each of the above cycles does involve the release of many of the neurotransmitters we’ve already discussed (dopamine, serotonin, etc.).

In fact, there seem to be three major area in the brain that are activated during sex:

  1. The Medial Preoptic Area (MPOA) – This is one of the areas where all the sensory inputs to the brain converge. This. This area is crucial for the initiation of sexual response – the move from desire to arousal. It is mostly the release of dopamine within this area that supports sexual responding. Animals with lesions here can’t  mount or thrust.
  2. Paravantricular  (male) or ventromedial hypothalamus – These area are responsible for non-contact sexual responses. Dopamine is once again the main activating agent here.
  3. The mesolimbic system – Important for the motivation towards anything “good” this system is also very involved in motivation for sex, a big part of the desire and arousal stages. As with drugs, it is the release of dopamine with this system that increases the motivation for sex.

We haven’t discussed the first two area much, and from my understanding, their functioning is relatively specific to sexual response. However, we’ve certainly mentioned the mesolimbic system. This is the same system involved in the brain’s processing of opiates, cocaine, methamphetamine, and essentially all other drugs. It is also the system in charge of food motivation.

As you can see, dopamine is an activating neurotransmitter for sexual response. Serotonin on the other hand, plays an inhibitory role in sex. Through its activity on a number of brain area, serotonin reduces desire, arousal, as well as the ability to orgasm. The increase of overall brain-serotonin levels is one of the main reasons for reduced sexual responsivity in individuals who are taking SSRI antidepressants.

What about sex addiction?!

Aside from a few specific authors (like P. Carnes), scientists still find themselves struggling with whether or not behavioral addictions should be considered similar to drug and alcohol addiction or whether they are examples of compulsive, or impulsive, behaviors. I personally believe that these all share more common features than we may yet realize.

Nevertheless, for addicts, the subjective experience of a substance, or behavioral, addiction is similar. It is an inability  to control a behavior in the face of repeated negative consequences that is often accompanied by a need for more and a reduced sensitivity to the act.

Given my recent reading on the brain processes involved in normal human sexual response, I’ve developed my own early theory about sex addiction:

Given that many of the same neurotransmitters are involved in the regulation of sex, it is my belief that sexual addicts or those experiencing sexual compulsions, fall into one of two categories that probably overlap to some extent:

  1. Individuals who have reduced inhibitory capacity (like those with impulse control disorder, ADD, or ADHD for example). These individuals find themselves acting out relatively impulsive behaviors that others without such dysfunction seem to effortlessly control. Given what we know about impulse control disorders, it is no wonder that these individuals often find themselves engaging in more than one such behavior, including drug, sex, and other poossibly addictive activities.
  2. Those who’ve had sex paired with a strong neurological response – Given the important role of dopamine in all rewarding activities (what scientists call appetitive response), it is very possible that two or more rewarding experiences that are linked may increase the brain’s response to any of the individual rewards.

neurons that fire togetherLet me explain the last point: In neuroscience, there’s the concept that Neurons that fire together wire together,” which is to say that events that happen at the same time, if they are strong enough, may form their own neural networks. If something strongly negative (like violence) happens in conjunction with sex, the experience might lower sex responsivity. However, if a strongly rewarding event happens at the same time, the link might serve to enhance response for both future sexual experiences and the linked event.  The people in the first group are likely to often fall into this category due to their use of psychoactive substances. Drugs release huge amounts of dopamine, which may then become linked with sexual response, making sex seeking as strong as drug seeking.

So that’s my take, for now, on sex addiction. Like other addictions, it has to do with the exposure to a very rewarding event that in a subset of individuals ends up developing an exaggerated response or an inability to control it. Since feeling of love and intimacy can often be just as rewarding, people often refer to themselves as love addicted, and not sex addicted.

Sources:

1) A. G., Resnick, & M. H. Ithman (2008). The Human Sexual Response Cycle: Psychotropic Side Effects and Treatment Strategies. Psychiatric Annals, 38, pp. 267-280.

2) E. M. Hull, D. S. Lorrain, J. Du, L. Matuszewich, L. A. Lumley, S. K. Putnam, J. Moses (1999) Hormone-neurotransmitter interactions in the control of sexual behavior. Behavioral Brain Research, 105, 105-116.