Consideration of sex as a biological variable in the translation of pharmacotherapy for stress-associated drug seeking

The near-miss effect in gambling behaviour occurs when an outcome which is close to a win outcome invigorates gambling behaviour notwithstanding lack of associated reward. In this paper I postulate that the processing of concepts which are deemed controllable is rooted in neurological machinery located in the posterior parietal cortex specialised for the processing of objects which are immediately actionable or controllable because they are within reach. I theorise that the use of a common machinery facilitates spatial influence on the perception of concepts such that the win outcome which is 'almost complete' is perceived as being 'almost within reach'. The perceived realisability of the win increases subjective reward probability and the associated expected action value which impacts decision-making and behaviour. This novel hypothesis is the first to offer a neurological model which can comprehensively explain many empirical findings associated with the near-miss effect as well as other gambling phenomena such as the ‘illusion of control’. Furthermore, when extended to other compulsive behaviours such as drug addiction, the model can offer an explanation for continued drug-seeking following devaluation and for the increase in cravings in response to perceived opportunity to self-administer, neither of which can be explained by simple reinforcement models alone. This paper therefore provides an innovative and unifying perspective for the study and treatment of behavioural and substance addictions.

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Faculty Opinions recommendation of Review. Neural mechanisms underlying the vulnerability to develop compulsive drug-seeking habits and addiction.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1119807.575900 ◽

2008 ◽

Author(s):

Kent Berridge

Keyword(s):

Neural Mechanisms ◽

Drug Seeking

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Walking speed declines with age in male and female baboons ( Papio sp .): Confirmation of findings with sex as a biological variable

Journal of Medical Primatology ◽

10.1111/jmp.12538 ◽

2021 ◽

Author(s):

Hillary F. Huber ◽

Kenneth G. Gerow ◽

Cun Li ◽

Peter W. Nathanielsz

Keyword(s):

Walking Speed ◽

Male And Female ◽

Biological Variable

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The Drug-Seeking Patient in the Emergency Room

Emergency Medicine Clinics of North America ◽

10.1016/j.emc.2004.12.006 ◽

2005 ◽

Vol 23 (2) ◽

pp. 349-365 ◽

Cited By ~ 43

Author(s):

George R. Hansen

Keyword(s):

Emergency Room ◽

Drug Seeking

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Care plans reduce ED visits in those with drug-seeking behavior

The American Journal of Emergency Medicine ◽

10.1016/j.ajem.2015.08.038 ◽

2015 ◽

Vol 33 (12) ◽

pp. 1799-1801 ◽

Cited By ~ 2

Author(s):

Frederick Fiesseler ◽

Renee Riggs ◽

David Salo ◽

Richard Klemm ◽

Ashley Flannery ◽

...

Keyword(s):

Drug Seeking ◽

Care Plans ◽

Seeking Behavior ◽

Ed Visits

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Sex differences in type and occurrence of adverse reactions to opioid analgesics: a retrospective cohort study

BMJ Open ◽

10.1136/bmjopen-2020-044157 ◽

2021 ◽

Vol 11 (6) ◽

pp. e044157

Author(s):

Guilherme S Lopes ◽

Suzette Bielinski ◽

Ann M Moyer ◽

Debra J Jacobson ◽

Liwei Wang ◽

...

Keyword(s):

Nervous System ◽

Sex Differences ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Adverse Reactions ◽

Secondary Outcome ◽

Opioid Prescription ◽

Biological Variable ◽

The Right

ObjectivesSex as a biological variable affects response to opioids. However, few reports describe the prevalence of specific adverse reactions to commonly prescribed opioids in men and women separately. A large cohort was used to investigate sex differences in type and occurrence of adverse reactions associated with use of codeine, tramadol, oxycodone and hydrocodone.DesignRetrospective cohort study.SettingParticipants in the Right Drug, Right Dose, Right Time (RIGHT) Study.ParticipantsThe medical records of 8457 participants in the RIGHT Study who received an opioid prescription between 1 January 2004 and 31 December 2017 were reviewed 61% women, 94% white, median age (Q1–Q3)=58 (47–66).Primary and secondary outcome measuresAdverse reactions including gastrointestinal, skin, psychiatric and nervous system issues were collected from the allergy section of each patient’s medical record. Sex differences in the risk of adverse reactions due to prescribed opioids were modelled using logistic regression adjusted for age, body mass index, race and ethnicity.ResultsFrom 8457 participants (of which 449 (5.3%) reported adverse reactions), more women (6.5%) than men (3.4%) reported adverse reactions to at least one opioid (OR (95% CI)=2.3 (1.8 to 2.8), p<0.001). Women were more likely to report adverse reactions to tramadol (OR (95% CI)=2.8 (1.8 to 4.4), p<0.001) and oxycodone (OR (95% CI)=2.2 (1.7 to 2.9), p<0.001). Women were more likely to report gastrointestinal (OR (95% CI)=3.1 (2.3 to 4.3), p<0.001), skin (OR (95% CI)=2.1 (1.4 to 3.3), p=0.001) and nervous system issues (OR (95% CI)=2.3 (1.3 to 4.2), p=0.004).ConclusionsThese findings support the importance of sex as a biological variable to be factored into pain management studies.

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Engineering Safer Psychedelics for Treating Addiction

Neuroscience Insights ◽

10.1177/26331055211033847 ◽

2021 ◽

Vol 16 ◽

pp. 263310552110338

Author(s):

Jamie Peters ◽

David E Olson

Keyword(s):

Executive Control ◽

Neural Circuitry ◽

Opioid Addiction ◽

Adult Brain ◽

Great Promise ◽

Therapeutic Effects ◽

Preclinical Models ◽

Drug Seeking ◽

Reward Circuitry

Addiction is best described as a disorder of maladaptive neuroplasticity involving the simultaneous strengthening of reward circuitry that drives compulsive drug seeking and weakening of circuits involved in executive control over harmful behaviors. Psychedelics have shown great promise for treating addiction, with many people attributing their therapeutic effects to insights gained while under the influence of the drug. However, psychedelics are also potent psychoplastogens—molecules capable of rapidly re-wiring the adult brain. The advent of non-hallucinogenic psychoplastogens with anti-addictive properties raises the intriguing possibility that hallucinations might not be necessary for all therapeutic effects of psychedelic-based medicines, so long as the underlying pathological neural circuitry can be remedied. One of these non-hallucinogenic psychoplastogens, tabernanthalog (TBG), appears to have long-lasting therapeutic effects in preclinical models relevant to alcohol and opioid addiction. Here, we discuss the implications of these results for the development of addiction treatments, as well as the next steps for advancing TBG and related non-hallucinogenic psychoplastogens as addiction therapeutics.

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