A substantial body of research has accumulated over several decades and transformed our understanding of substance use and its effects on the brain. This knowledge has opened the door to new ways of thinking about prevention and treatment of substance use disorders. For example, alcohol can cause an alternative form of a gene to be expressed in the memory circuits in flies and people, resulting in changes in dopamine receptors and transcription factors involved in reward signaling and neuronal function. Similarly, cocaine can cause an alternative form of a gene to be expressed in the reward centers of mice, leading them to seek out more cocaine.

Such research has the potential to identify common neurobiological mechanisms underlying substance use disorders, as well as other related mental disorders. This research is expected to reveal new neurobiological targets, leading to new medications and non-pharmacological treatments—such as transcranial magnetic stimulation or vaccines—for the treatment of substance use disorders. A better understanding of the neurobiological mechanisms underlying substance use disorders could also help to inform behavioral interventions. Female rats, in general, learn to self-administer drugs and alcohol more rapidly, escalate their drug taking more quickly, show greater symptoms of withdrawal, and are more likely to resume drug seeking in response to drugs, drug-related cues, or stressors. The one exception is that female rats show less withdrawal symptoms related to alcohol use.74 Researchers are investigating the neurobiological bases for these differences.

An Evolving Understanding of Substance Use Disorders

For example, some drugs, such as marijuana and heroin, have a similar structure to chemical messengers, called neurotransmitters, which are naturally produced by the brain. These drugs can fool the brain’s receptors and activate nerve cells to send abnormal messages because of this similarity. Other drugs, such as cocaine or methamphetamine, can cause the nerve cells to release abnormally large amounts of natural neurotransmitters or prevent the regular recycling of these brain chemicals, which alcohol vs drugs is needed to shut off the signal between neurons. This disruption produces a greatly amplified message that results in a different type of high. Some investigators have hypothesized that functions controlled by the brain’s right hemisphere are more vulnerable to alcoholism-related damage than those carried out by the left hemisphere (see Oscar-Berman and Schendan 2000 for review). The left hemisphere has a dominant role in communication and in understanding the spoken and written word.

Longitudinal data on cannabis use and neuropsychological development are generally lacking. Preliminary evidence suggests that heavy to very heavy use could lead to deteriorated development of executive functions and IQ. Heavy alcohol and cannabis co-use in adolescence has been linked to a range of deficits, including deficits in attentional control, learning and memory, visuospatial functioning, and psychomotor speed.

Neural Systems Affected and Concomitant Neurobehavioral Deficits

Addiction is a brain disease that causes physical and physiological changes to the brain. The brain controls our thoughts, memory and speech, movement of the limbs, and the function of many organs within our body. Drugs and alcohol affect the brain’s neurotransmitters, which release an excess level of dopamine, causing temporary pleasurable feelings and euphoria. The brain eventually adapts to the quantity of drugs or alcohol used, making the sought-after substance or activity less pleasurable. White matter integrity following alcohol and cannabis use was examined in six studies, including four alcohol use studies and two alcohol and cannabis co-use studies. Drugs affect the brain’s neurons, they affect communication between the brain and different parts of the body, similar to alcohol.

• Structural imaging techniques allow one to examine the brain’s physical, anatomical structure.
• At the behavioral level, alcohol intoxication has been shown to increase risky behaviors such as risky driving, criminal behavior, and sexual promiscuity [108], whilst trait impulsivity has often been found to be increased in alcohol dependent individuals [109].
• Nedergaard and her colleagues discovered in 2012 that the cerebral spinal fluid (CSF) that surrounds the brain and spinal cord isn’t just a cushion against shocks.
• In flies, a high sugar diet can reprogram the ability to taste sweetness by tapping into a gene expression network involved in development.

Amnesia, especially anterograde amnesia, or memory loss for recent events, is an intriguing and serious disorder. Patients with Korsakoff’s syndrome are permanently unable to remember new information for more than a few seconds. Because new events are forgotten a few seconds after they occur, virtually nothing new is learned, and patients with Korsakoff’s syndrome live perpetually in the past. However, in contrast to patients with alcoholic dementia, who have generalized cognitive decline (including widespread memory loss), patients with Korsakoff’s syndrome retain old memories formed prior to the onset of alcohol-related brain damage.

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Harper (1998) and his collaborators established that 15–23% of cortical neurons are selectively lost from the frontal association cortex following chronic alcohol consumption. Frontal lobe blood flow (Nicolás et al. 1993) and metabolism (Volkow et al. 1992, 2002) may decrease in alcoholics before significant shrinkage or major cognitive problems become detectable (Nicolás et al. 1993; Wang et al. 1993). A wealth of longitudinal studies have assessed the effect of adolescent alcohol and cannabis use on neuropsychological development.

Meanwhile, the current pharmacological therapies are only modestly effective in preventing relapse and dependence in alcoholics (Doggrell 2006; Kranzler and Van Kirk 2001; Mann 2004), prompting more research. Additionally, treating co-occurring disorders remains a challenge, and the use of creative approaches that would encompass individualized psychosocial support, as well as a combination of treatments, might be the most effective way to address this problem. Prefrontal neurobehavioral dysfunction has been frequently observed in alcoholics with and without the dense amnesia of Korsakoff’s syndrome (Dirksen et al. 2006; Gansler et al. 2000; Oscar-Berman and Evert 1997; Oscar-Berman et al. 2004).

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Animal and human studies build on and inform each other, and in combination provide a more complete picture of the neurobiology of addiction. The rest of this chapter weaves together the most compelling data from both types of studies to describe a neurobiological framework for addiction.

• This research is expected to reveal new neurobiological targets, leading to new medications and non-pharmacological treatments—such as transcranial magnetic stimulation or vaccines—for the treatment of substance use disorders.
• It is important to keep in mind, however, that frontal brain systems are connected to other regions of the brain, and frontal abnormalities may therefore reflect pathology elsewhere (Moselhy et al. 2001).
• However, there is a dearth of careful studies of the complex interactions between alcohol intoxication and the multifaceted construct of aggression.

Obviously, there is still too little specific information available in the scientific literature to predict what will happen when both of these drugs are present in the brain. Sadly, due to a total lack of knowledge, combining marijuana and alcohol is still a pharmacological roulette. 1Alcohol dependence, also known as alcoholism, is characterized by a craving for alcohol, possible physical dependence on alcohol, an inability to control one’s drinking on any given occasion, and an increasing tolerance to alcohol’s effects (American Psychiatric Association [APA] 1994).

Synthetic Drugs

Alcohol use is typically initiated during adolescence, and studies have found that alcohol can impact neurodevelopmental trajectories during this period. Typical brain maturation can be characterized as a loss in grey matter density due to synaptic pruning alongside ongoing growth of white matter volume that reflects increased myelination to strengthen surviving connections [49]. These effects are found in prefrontal, cingulate, and temporal regions as well as the corpus callosum and may reflect an acceleration of typical age-related developmental processes similar to what we have described in adults with alcohol dependence. Less is known about the dose-response mechanism, though it has been suggested moderate drinking lies somewhere intermediate [52,53]. This would again imply that the impact of alcohol consumption on brain structure is not limited to heavy alcohol consumption. However, it has been noted there are differences in brain structure that predate alcohol initiation and may predispose individuals to heavy alcohol use.

The binge/intoxication stage of the addiction cycle is the stage at which an individual consumes the substance of choice. This stage heavily involves the basal ganglia (Figure 2.4) and its two key brain sub-regions, the nucleus accumbens and the dorsal striatum. Seven previously described studies have examined the impact of alcohol and cannabis use on visual processing ability across adolescence, including four alcohol-focused studies and three co-use studies. Attentional control has been measured in two longitudinal studies focused on the effects of low to heavy alcohol use; in two studies focused on effects of heavy cannabis use; and in three studies exploring co-use of alcohol and cannabis.