Author: James Anderson

Understanding Reverse Tolerance to Drugs and Alcohol

In some cases drug sensitization may also refer to medical interventions (e.g. a drug holiday) that aim to reduce the insensitivity caused by drug tolerance. In doing so, they put themselves at a heightened risk for a life-threatening overdose because they are unaware that toxicity levels are higher than they actually are. This effect can also manifest when an individual who is high or intoxicated encounters sudden and dramatic/traumatic circumstances. In this situation, the brain can rapidly refocus on the threatening event, and the high will be reduced or effectively eliminated. Most people are not aware that there are actually several forms of tolerance to substances, each of which has some effect on the processes of addiction. It is true that tolerance often leads many people who are vulnerable to addiction to use increasing amounts of a substance to fulfill their needs.

Study 3 was a semi-naturalistic laboratory study with real-time assessments of hangover severity. Recently, Köchling et al. 10 examined the impact of the sequence of consuming beer and wine on hangover severity in 90 participants. Overall hangover severity was assessed as a composite score of eight individual items, including thirst, fatigue, headache, dizziness, nausea, stomach ache, tachycardia, and loss of appetite. The intensity of these symptoms was scored on a seven-point scale, with the sum score representing the overall hangover severity ranging from 0 (absent) to 56 (extreme hangover).

In a pig model, chronic nitrate administration decreased the number of NO-producing neurons in the brain stem with a loss of inhibitory effects of NO on sympathetic excitability.44 These phenomena could contribute to nitrate tolerance. Interestingly, repeated treatment with dopamine mimetic drugs, such as amphetamine, cocaine and even L-DOPA, also results in the behavioral supersensitivity often referred to in this literature as sensitization. The important factor in this treatment appears to be the intermittent nature of the drug administration. Continuous administration of L-DOPA or amphetamine through a pump will give the expected downregulation in dopamine receptor activity.

Physiology of alcohol tolerance

If the drug is stopped, it may take a long time period for the body to recover. In some cases of extreme tolerance build-up, sudden withdrawal of the drug can be fatal. In the case of marihuana, there seems to be a sort of “reverse tolerance” taking place. Some users report that they don’t need to take more and more marihuana to achieve the same effects and, in some cases, they can decrease the dosage. It may be that the reactions that a person has to taking marihuana may be partly learned behavior and it takes time to learn to expect certain reactions.

Repeated Antagonist Treatment

Future research should further investigate the relationship between hangover frequency and severity and alcohol use disorder and its implications for prevention. This may have an impact on the relationship between hangover frequency and hangover severity. Tolstrup et al. 24 also reported that during adulthood (18–65 years old) with increasing age, the frequency of hangovers gradually ameliorates. Although the title of the paper suggests otherwise, a closer look at the data revealed that they did not assess hangover severity. The observation that the occurrence of hangovers declined with increasing age persisted after correction for the usual amount of alcohol intake, frequency of binge drinking, and the proportion of alcohol consumed with meals. There are various socioeconomic and cultural factors that may contribute to the reduction in hangover frequency when age progresses.

Reducing Alcohol Tolerance

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Sensitization refers to an increased potency of a drug with repeated exposures to that drug (i.e., decrease in the ED50). According to this viewpoint, an increase in the way CNS receptors respond to the drug occurs after repeated drug exposures. Nevertheless, the obvious candidates are an up-regulation of receptors (i.e., more) or an increase in receptor affinity or efficacy. This phenomenon is most readily shown with stimulant drugs like amphetamine or cocaine. Some evidence points to the possibility of behavioral or learned sensitization. A related phenomenon, reverse tolerance, refers to an increase in a drug’s potency with repeated exposure due to toxic reactions, disease state, or organ damage.

Although hangover is a common consequence of heavy alcohol consumption, the area is heavily under-researched. Hangover frequency is a potential predictor of future alcohol use disorder that may be affected by hangover severity, yet the relationship between hangover frequency and severity has not been investigated. Using different methodologies and assessment instruments, two surveys, and one naturalistic study collected data on hangover frequency, hangover severity, and alcohol consumption.

  1. The toxicologist must know what drugs were taken and what drugs were already present when another one is taken and must be aware of synergistic effects.
  2. Interestingly, repeated treatment with dopamine mimetic drugs, such as amphetamine, cocaine and even L-DOPA, also results in the behavioral supersensitivity often referred to in this literature as sensitization.
  3. Personality was assessed with the Brief Symptom Inventory (BSI) 19 and the RT18 risk-taking questionnaire 20.
  4. At this point, driving may be a death sentence even without the awareness of the drinker.
  5. Multiples lines of evidence now support the primacy of insulin as the initiating autoantigen in T1D.

Results

Drugs can have undesired interactions through pharmacokinetic or pharmacodynamic mechanisms. These interactions can vary widely in their potential to cause serious problems. Tricyclic antidepressive drugs can produce potential hazardous interactions when combined with MAOIs, NE, Epi, or phenothiazines. Drug overdosing could result from certain classes of drug interactions but more commonly results from the patient’s deliberate attempt at suicide. See Kaplan and Sadock (1996), Hughes and Pierattini (1992), or Gelenberg and Bassuck (1997) for the diagnosis and treatment guidelines for these drug effects. This effect results in an individual requiring increasingly higher doses of the substance to achieve the desired effect.

The apoptotic pathway of deletional tolerance involves the Bcl-2 family member Bim, which induces the release of cytochrome c and entry into the caspase cascade 8. Physical dependence refers to a general physiological adaptation to chronic drug exposure, usually manifested during withdrawal from the drug (see Henningfield, Schuh, & Jarvik, 1995). The chronic withdrawal or abstinence syndrome involves physiological, subjective, and cognitive symptoms. For example, sedative/hypnotics, like alcohol, BZDs, and morphine, generally produce an excitable withdrawal profile. On the other hand, stimulants like cocaine or amphetamine generally produce depressive or lethargic withdrawal symptoms. These data suggest an opponent-process, rebound pattern of withdrawal symptoms.

We may be paid a fee for marketing or advertising by organizations that can assist with treating people with substance use disorders. I have worked in the substance abuse treatment field and I sent my own Mother to Silver Ridge to recover. The Five-Shot questionnaire alcohol screening test was used to detect heavy drinking 18. It is a short, self-report inventory, composed of two questions from the Alcohol Use Disorders Identification Test (AUDIT) 21,22 and three questions from the CAGE test 23. It consists of 53 items; each rated on a five-point scale of distress from 1 (not-at-all) to 5 (extremely). The instrument is scored on nine symptom dimensions; somatization, obsession-compulsion, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism.

Getting Help for Addiction

While the origin of this anergic state is unclear, the presence of an anergic or anergy-like state may allow islet-specific clones to persist in the periphery and escape deletional tolerance from steady-state DC presenting cognate antigen. The residual presence of these cells presents an ongoing danger while they may ultimately be reactivated and become pathogenic. Contact-dependent effector T cell suppression can also be mediated through the PD1/PD-L1 pathway independently of Tregs.