(Some of) The determinants of tobacco addiction
Sean P Barrett 1988 Surgeon General Report
• Cigarettes and other forms of tobacco are addicting.
• Nicotine is the drug in tobacco that causes addiction.
• The processes that determine tobacco addiction are similar to those that determine addiction to drugs such as heroin and cocaine.
Why nicotine? abundant constituent of tobacco smoke
has central effects; modulates dopamine
animal models suggest reinforcing effects
nicotinic drugs impact smoking
pharmacokinetics of delivery via smoking
Why not acetaldehyde? abundant constituent of tobacco smoke
has central effects; modulates dopamine
animal models suggest reinforcing effects
alcohol impacts smoking
pharmacokinetics of delivery via smoking
From Philip Morris laboratories:
E-liquids contain a mixture of propylene glycol, vegetable glycerin, and flavoring that when heated can produce acetaldehyde
In addition to nicotine, e- liquids have been shown to contain other psychoactive alkaloids (e.g. anabasine, nornicotine) Tobacco is more than nicotine and acetaldehyde… • Tobacco contains ~1000 constituents (~5000 in tobacco smoke); some with independent psychoactive and/or reinforcing effects (e.g. anabasine, anabatine, cotinine, nornicotine). • When two or more compounds are simultaneously administered there is the potential for interactions • Smoking also involves non-pharmacological aspects – Social, Behavioral, Sensory, Situational, Psychological etc. Behavioural Pharmacology 2010, 21:144–152 NT=DT< NI=PI NI
NT=Nicotine Tobacco; DT=Denicotinized Tobacco; NI=Nicotine Inhaler; PI=Placebo Inhaler Is addiction to tobacco similar to addiction to drugs such as heroin and cocaine? DSM V-Substance use disorders DSM V WITHDRAWAL SYMPTOMS (Criterion B)
PHYSICAL/NEUROLOGICAL PSYCHOLOGICAL / SUBJECTIVE A Autonomic hyperactivity; Insomnia; Anxiety L C Nausea/vomiting; O Hand tremor; Psychomotor H O agitation; Generalized tonic-clonic L seizures; Hallucinations
C Flu like symptoms; Headache Dysphoric /depressed mood or A F irritability; Difficulty concentrating; F Fatigue E I N E
C Weight loss; Abdominal pain; Irritability, anger/ aggression; A N Shakiness/tremors; Sweating; Anxiety/ Nervousness; Sleep N Fever, Chills or Headache difficulties; Decreased appetite; A B Restlessness; Depressed mood I S
WITHDRAWAL SYMPTOMS
PHYSICAL/NEUROLOGICAL PSYCHOLOGICAL/SUBJECTIVE O Nausea/vomiting; Muscle Dysphoric mood; Insomnia P I Aches; Lacrimation or O rhinorrhea; Pupillary dilation; I D Piloerection or sweating; S Diarrhea; Yawning; Fever
S Psychomotor retardation or Dysphoric mood; Insomnia or T I agitation; Vivid, Unpleasant hypersomnia, Increased appetite M dreams U L A N T S
T Irritability; Restlessness; Depressed O B mood; Frustration or anger; Anxiety; A Difficulty concentrating; Increased C C appetite; Insomnia O
NON-DRUG WITHDRAWAL • Internet gaming – Irritability, Anxiety, Sadness (DSM V-condition for further study) • Gambling – Irritability, Restlessness (DSM V) • Relationship loss – Irritability, Anxiety, Restlessness; Trouble Concentrating, Depression (Gilbert et al. 1998) • Junk food – Irritability, Anxiety, Sadness, fatigue (Schulte et al. 2018)
Is there a physiological basis for tobacco related withdrawal and craving?
The impact of actual and perceived nicotine administration on insula related activity
L. Anterior Insula-dACC R. Anterior Insula-dACC Told placebo 0.4 0.4 Told placebo Told nicotine Told nicotine
0.3 0.3
0.2 0.2
0.1 0.1
COPE means COPE 0 COPE means COPE 0
-0.1 -0.1
-0.2 -0.2 Given Placebo Given Nicotine Given Placebo Given Nicotine
Perry, Schlagintweit & Barrett in preparation Need for non-pharmacological interventions: Acknowledgements