International Journal of Neuroscience
ISSN: 0020-7454 (Print) 1543-5245 (Online) Journal homepage: http://www.tandfonline.com/loi/ines20
Cocaine Addiction: Relationship to Seasonal Affective Disorder Reuven Sandyk & J. Daniel Kanofsky To cite this article: Reuven Sandyk & J. Daniel Kanofsky (1992) Cocaine Addiction: Relationship to Seasonal Affective Disorder, International Journal of Neuroscience, 64:1-4, 195-201, DOI: 10.3109/00207459209000545 To link to this article: http://dx.doi.org/10.3109/00207459209000545
Published online: 07 Jul 2009.
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Date: 10 May 2016, At: 11:38
Infern. J . Neuroscience, 1992, Vol. 64, pp. 195-201 Reprints available directly from the publisher Photocopying permitted by license only
0 1992 Gordon and Breach Science Publishers S . A . Printed in the United States of America
ChicaZ Note COCAINE ADDICTION: RELATIONSHIP TO SEASONAL AFFECTIVE DISORDER REUVEN SANDYK and J . DANIEL KANOFSKY Department of Psychiatry, Albert Einstein College of Medicine/Montefore Medical Center, Bronx, New York, NY 10461, U.S.A.
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(Received December 20, 1990; in final form February 7 , 1992)
We report a 25 year-old patient with seasonal affective disorder (SAD) and cocaine abuse who experienced cyclical fluctuations in cocaine craving which were concomitant with seasonal alterations in mood. The temporal association of both disorders in this patient suggests that they may share a common underlying pathophysiology . Since disturbances in circadian rhythms and pineal melatonin functions may in part underlie the pathophysiology of SAD and the psychomimetic effects of cocaine are mediated in part through the pineal gland, we propose that dysfunction of circadian rhythms and pineal melatonin functions may partly mediate the association of SAD with cocaine abuse. This hypothesis may have potential clinical and therapeutic implications for a subgroup of cocaine abusers with SAD since light therapy, which is efficacious in the therapy of SAD, may also prove to be beneficial in reducing cocaine addiction. Furthermore, the report illustrates the need for investigations of environmental cues for cocaine abuse with specific attention given to the effects of light on circadian mood changes. Keywords: Cocaine use, pineal gland, seasonal affective disorder.
Epidemiological studies demonstrate that cocaine abuse has grown to epidemic proportions in the United States (Kay et al., 1990; Regier et al., 1990). This is especially true in the mentally ill. A recent epidemiologic study found that 20% of individuals with mental disorders also carry a current diagnosis of substance abuse disorder. Moreover, as many as 29% of all persons with mental disorders have a lifetime diagnosis of substance abuse disorder (Regier et al., 1990). For schizophrenia, the lifetime rate of substance dependence/abuse is 47% and for bipolar disorder, the rate increases to 56% (Regier et al., 1990). The latter findings suggest a causal or secondary relationship between substance abuse/dependence and the pathophysiology of affective disorders. Theories attempting to address the complex interaction between the abuse of psychoactive substances and psychopathology have commented on both substance abuse being the cause of psychiatric symptoms and use of drugs of abuse reflecting “selfmedication” for psychiatric symptoms (McLellan & Druley, 1977). For instance, the rewarding effect of cocaine is thought to be related to an increase in mesolimbic dopaminergic activity (Ellinwood & Gawin, 1988), which may explain its widespread use in patients with various psychiatric disorders associated with disturbances in central dopaminergic functions (Regier et al., 1990). Recent studies have linked the pathophysiology of affective disorders with disturbances in circadian rhythms and pineal melatonin functions (cf. Miles & Philbrick, Correspondence to: Prof. Reuven Sandyk, M.D., M.Sc. P.O. Box 203, Bedford Hills, NY, 10507, USA. 195
196
R. SANDYK AND J.D. KANOFSKY TABLE 1 Evidence Implicating the Pineal Gland in Substance Abuse Disorder
cocaine increases melatonin production the pineal gland mediates the effects of hallucinogenic psychomimetic drugs large amounts of melatonin are present in regions involved in reward mechanisms abnormal pineal functions occur in heroin addicts 5. lithium carbonate stimulates melatonin secretion and decreases cocaine craving 6. desipramine phase shifts melatonin secretion and attenuates cocaine craving 7 . melatonin reduces anxiety and produces feelings of contentment and general mood elevation
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1. 2. 3. 4.
1988). Melatonin secretion has been found to be reduced in bipolar affective disorder patients (Lewy et al., 1979). In addition, these patients demonstrate supersensitivity to light (Lewy et al., 1981). The effects of some antidepressant drugs in depressive illness may be related to their capacity to stimulate melatonin secretion (cf. Miles & Philbrick, 1988), while the efficacy of lithium carbonate in the prophylaxis of manic-depressive illness may be secondary to its ability to stimulate and/or phase delay melatonin secretion (Yocca et al., 1983; Touitou et al., 1987). Disturbances in melatonin secretion and functions may also underlie in part some of the symptoms of seasonal affective disorder (SAD) (Rosenthal et al., 1984; Rosenthal et al., 1986; Wehr & Rosenthal, 1989), a specific ‘biological’ subtype of affective illness (Thompson & Isaacs, 1988), which is characterised by seasonal patterns of depression during which time patients frequently experience an increased desire to sleep and increased appetite for carbohydrate rich foods during the autumn or winter months (Rosenthal et al., 1984; Wehr & Rosenthal, 1989). Since substance abuse is particularly common among patients with affective disorders, and since melatonin is implicated in the pathophysiology of at least some depressive illnesses, it is possible that disturbances in pineal melatonin functions may also underlie some substance abuse disorders. This notion is supported by the following observations (see Table 1): (a) cocaine and amphetamines increase melatonin production in rats (Backstrom & Wetterberg, 1973; Holtz et al., 1974), (b) the integrity of the pineal gland is necessary for the hallucinogenic manifestations of various hallucinogenic psychomimetic drugs such as LSD and mescaline (Winters et al., 1973), (c) relatively large amounts of immunoreactive melatonin are present in the nucleus accumbens (Seguela et al., 1982), a critical structure in the reward system (Bozarth, 1987), (d) abnormal pineal melatonin functions have been reported in heroin addicts (Esposti et al., 1986), (e) lithium carbonate, which stimulates and/ or phase shifts melatonin secretion in humans (Touitou et el., 1987), reportedly attenuates cocaine abuse in bipolar patients (Kleber & Gawin, 1984) and desipramine, which specifically attenuates cocaine craving (Gawin & Kleber, 1984; Satel & Gawin, 1989), phase shifts melatonin secretion in humans (Touitou et al., 1987), and (f) oral administration of melatonin reduces anxiety and produces feelings of contentment and general mood elevation (Anton-Tay et al., 1971; Shaw et al., 1973; Cramer et al., 1974). Although the precise role of the pineal gland in humans is largely elusive, there is evidence that it is involved in the regulation of circadian and seasonal variations of various biological functions. Involvement of the pineal gland in addictive behavior (cf. Sandyk, 1991) suggests that cocaine addiction may be influenced by seasonal changes. In fact, Rosenthal et al. (1983) reported cyclical “self-medication” with cocaine in patients with bipolar disorder and Satel and Gawin (1989) reported two patients with seasonal affective disorder in whom fluctuations in cocaine abuse par-
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alleled the occurrence of seasonal dysphoria. In both patients cocaine abuse increased significantly during the fall and winter and declined spontaneously during the summer months. We present an additional patient with mild SAD in whom seasonal alterations in cocaine abuse paralleled spontaneous fluctuations in mood, sleep, appetite, and cognitive functions. We propose that in this patient the coexistence of SAD and cocaine abuse may have been mediated by a common underlying pathophysiological mechanism involving abnormal regulation of circadian rhythms and possibly associated with dysfunction of the pineal gland.
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CASE REPORT This 25 year-old single black man was admitted to the Bronx Psychiatric Center in New York City in October of 1989 with a diagnosis of substance abuse disorder and episodic cocaine-induced psychosis. His drug use dates back to 1978, when at the age of 13, he first began to use marijuana and phencyclidine (PCP). Since the age of 16 he had been using cocaine regularly and more recently, crack cocaine. The patient had normal developmental milestones and he was an average student in school. He dropped out of high school in the 10th grade as a result of excessive drug use which was associated with episodes of cocaine-related psychosis. Since then he had had multiple hospitalizations in numerous psychiatric facilities for cocaineinduced psychotic episodes and was treated with neuroleptic medication. In November of 1989 his addictive behavior worsened and his increased usage of crack cocaine had caused him to allegedly assault a woman on the subway and steal her gold chain. He was arrested and subsequently admitted to our institution under the provisions of CPL 730 Final Status. During his institutionalization he was treated with carbamazepine (800 mg/d) which attenuated his craving for cocaine. Unfortunately, the drug had to be discontinued owing to the development of first degree heart block which was judged to be secondary to carbamazepine. He is currently receiving no psychotrophic medication and random drug screens have found no evidence for cocaine use over the past year. A recent examination performed in mid-December of 1990 found him to be pleasant and cooperative. He was coherent, relevant, and oriented in the spheres of person, place, and time. His speech was normal in rate and rhythm. Hallucinations and delusions were denied. He admitted to “being a little sad” and staff members and the patient’s girlfriend commented that he was not as outgoing as usual. He denied suicidal or homocidal ideation; his affect was well modulated, and his judgment and insight were intact. A specific inquiry into his affect suggested that the patient may have suffered from mild SAD. Specifically, he reported experiencing distinct seasonal fluctuations in mood and other vegetative symptoms of depression since the age of 15 which preceded the use of cocaine; by mid-autumn and throughout the winter months he experienced hypersomnia, decreased concentration, loss of appetite, general apathy, decreased libido, lack of motivation, and inactivity. During the winter period he admitted to taking cocaine approximately 3-4 times per week and stated that he would have used cocaine even more frequently if it were financially possible. In contrast, with the onset of spring and during the summer months, he experienced elevation of mood, increased energy, improved concentration, decreased urge to sleep, increased libido, and increased appetite associated with weight gain of about 10 lb.
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He also reported a significant spontaneous decrease in cocaine craving and admitted to a cocaine use of once per week.
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DISCUSSION This case demonstrates an association between cocaine abuse and seasonal mood fluctuations in a patient with a mild form of SAD. The temporal relationship between cocaine abuse and seasonal changes in mood suggests that both disorders may share a common underlying pathophysiology. This notion is supported further by the observations that: (a) the dysphoric symptoms of SAD (Rosenthal et al., 1984) resemble those of cocaine withdrawal (Gawin & Ellinwood, 1988), (b) both appear to respond transiently to administration of cocaine (Satel & Gawin, 1989), and (c) both may be associated with dysregulation of dopaminergic reward and activation systems (Jacobsen et a]., 1987; Gawin & Ellinwood, 1988). The clinical criteria for SAD have been outlined by Rosenthal et al. (1984) and include: (a) a history of at least one episode of major depression as defined by the Research Diagnostic Criteria, (b) recurrent fall-winter depressions, at least two of which occurred during successive years, separated by nondepressed periods in spring and summer, (c) no other DSM-111 Axis I psychopathology, and (d) the absence of regularly occurring psychosocial variables that might account for the regular seasonal depressions. Although the above criteria are typical for SAD, many variations are seen and atypical forms of SAD may be more common than previously thought (Wehr & Rosenthal, 1989). A milder version of the condition has been reported to occur also in children and adolescents which also appears to respond to phototherapy (Rosenthal et al., 1985). The pathophysiology of SAD remains elusive. A recent report indicates that SAD is related to dysfunction deep in the right temporofrontal region (Hunt & Silverstone, 1990). According to the melatonin theory of SAD (Wehr & Rosenthal, 1989), which was inspired by animal studies of seasonal rhythms, changes in the length of the day trigger winter depression by modifying the pattern of nocturnal melatonin secretion, which acts as a chemical signal of darkness (Rosenthal et al., 1984). This hypothesis is supported in part by the findings of Lewy et al. (1987) revealing that the circadian rhythm phase in melatonin secretion is abnormally delayed in patients with winter depression. The circadian rhythm phase shijt hypothesis suggests that winter depression occurs when the circadian rhythm phases become abnormally delayed relative to sleep since dawn comes later (Wehr & Rosenthal, 1989). The circadian rhythm amplitude hypothesis suggests that winter depression is caused by a reduction in the amplitude of circadian rhythms and that light therapy attenuates winter depression by increasing the amplitude of circadian rhythms (Czeisler et al., 1987). An alternative possibility relates to the fact that since carbohydrate craving, an early and common feature of winter depression in patients with SAD, is linked to decreased serotonin (5-HT) metabolism (Wurtman et al., 1981), and since carbohydrate-rich diet increases brain 5-HT content (Femstrom & Wurtman, 1972), craving and other SAD symptoms are caused by a central 5-HT deficiency (Rosenthal & Heffernan, 1986). This hypothesis is consonant with the possibility that decreased melatonin functions may be related to winter depression in SAD since 5-HT is a precursor of melatonin. Moreover, since in experimental animals cocaine has been shown to increase melatonin secretion (Holtz et al., 1974), it is possible that in our patient cocaine abuse reflects a process of “self medication” aimed primarily at augmenting melatonin functions and therefore attenuating the winter depression in SAD.
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Thus, it is conceivable that the heightened abuse of cocaine during the winter time, when melatonin secretion is known to be reduced as a result of diminished light exposure, may reflect an endogenous mechanism aimed at increasing melatonin functions. However, the findings that bright light, which attenuates winter depression in patients with SAD (Wehr & Rosenthal, 1989), acutely inhibits human melatonin secretion (Lewy et al., 1980) argues against a direct relationship between decreased melatonin functions and winter depression in patients with SAD. Thus, clarification of the role of the pineal gland in SAD might shed further light on the relationships among SAD, cocaine abuse, and pineal melatonin functions. Light therapy is currently the most effective treatment for typical and atypical forms of SAD (Rosenthal et al., 1986; Lewy et al.. 1987; Wehr & Rosenthal, 1989). Since phototherapy is effective in the management of SAD, it is possible that it might also be effective in attenuating cocaine abuse in patients with SAD and its atypical forms. Moreover, since cholinergic drugs, such as carbachol, mimic the effects of light on the circadian rhythms in the rat pineal gland (Zatz & Brownstein, 1979), it is possible that drugs which increase cholinergic activity such as physostigmine and lecithin might attenuate cocaine abuse in patients with SAD, while agents with anticholinergic properties might exacerbate it. Recent epidemiological studies indicate that SAD is relatively common among patients with recurrent depression; prevalence rates of 16% to 38% have been cited in the literature (Thase, 1986; Garvey et al., 1988; Terman, 1988). In the general population, the prevalence of severe SAD is about 5% (cf. Wehr & Rosenthal, 1989). However, the incidence of mild SAD is significantly higher and it has been suggested that many individuals who neither meet criteria for major affective disorder nor seek treatment for their symptoms appear to experience mild SAD that interferes with their productivity and well being (cf. Wehr & Rosenthal, 1988). Given the high incidence of cocaine abuse in the general population, and particularly in patients with mental illness, it is conceivable that in a significant proportion of these patients, cocaine abuse may coexist with mild forms of SAD. Identification of these individuals could be important since light therapy may be a potentially effective modality in reducing cocaine abuse. Furthermore, the association between cocaine abuse with SAD indicates the need to develop investigations of environmental cues for cocaine addiction with special attention given to the effects of light on cyclical mood changes.
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Esposti, D., Esposti, G . , Lissoni, P., Mauri, R., Rovelli, F., Ruzsas, C. & Fraschini, F. (1986). A preliminary study of the pineal function in heroin addicts. Journal of Neural Transmission, 2I (SUPPI),492-493. Fernstrom, J. D. & Wurtman, R. J. (1972). Brain serotonin content: physiological regulation by plasma neutral amino acids. Science, 178. 414-416. Gaffori, O., Geffard, M. & van Ree, J. M. (1983). Des-Tyr'-gamma-endorphinand haloperidol increase pineal gland melatonin levels in rats. Peptides, 14, 393-395. Garvey, M. J., Wesner, R. & Codes, M. (1988). Comparison of seasonal and nonseasonal affective disorders. American Journal of P sychiatry. 145, 100- 102. Gawin, F. H. & Kleber, H. D. (1984). Cocaine abuse treatment: open pilot trial with desipramine and lithium carbonate. Archives of General Psychiatry, 4 1 , 903-909. Gawin, F. J . & Ellinwood, E. H. (1988). Cocaine and other stimulants: actions, abuse and treatment. New England Journal of Medicine, 318, 1173-1182. Holtz, R. W., Deguchi, T. C. & Axelrod, J. (1974). Stimulation of serotonin N-acetyltransferase in pineal organ culture by drugs. Journal of Neurochemistry, 22, 205-209. Hunt, N. & Silverstone, T. (1990). Seasonal affective disorder following brain injury. British Journal of Psychiatry, 156, 884-886. Jacobsen, F. M., Sack, D. A. B Wehr, T. A. (1987). Neuroendocrine response to 5-hydroxytryptophan in seasonal affective disorder. Archives of General P sychiarry, 4 4 , 1086- 1093. Lewy, A. J., Wehr, T. A., Gold, P. W. & Goodwin, F. K. (1979). Plasma melatonin in manic-depressive illness. In E. Usdin, J. J. Kopin & J. Barchas (Eds.). Carecholamines: basic and clinical frontiers. vol. 11, Oxford: Pergamon Press, pp. 1173-1175. Lewy, A. J., Wehr, T. A. & Goodwin, F. K. (1980). Light suppresses melatonin secretion in humans. Science, 210, 1267-1269. Lewy, A. J., Wehr, T. A., Goodwin, F. K., Newsome, D. & Rosenthal, N. E. (1981). Manic-depressive patients may be supersensitive to light. Lancer, I , 383-384. Lewy, A. J., Sack, R. L. & Miller, L. S. (1987). Antidepressant and circadian phase-shifting effects of light. Science, 235, 352-354. McLellan, A. T. & Druley, K. A. (1977). Non-random relation between drugs of abuse and psychiatric diagnosis. Journal of Psychiatric Research, 13, 179-184. Miles, A . & Philbrick, D. R. S. (1988). Melatonin and Psychiatry. Biological Psychiatry, 23, 405425. Regier, D. A., Farmer, M. E., Rae, D. S., Locke, B. Z . , Keith, S. J., Judd, L. L. & Goodwin, F. K. (1990). Comorbidity of mental disorders with alcohol and other drug abuse. Results from the epidemiologic catchment area (ECA) study. Journal qf the American Medical Association, 264, 2511-2518. Rosenthal, N. E. & Heffernan, M. M. (1986). Bulimia, carbohydrate craving, and depression: A central connections'? In R. J. Wurtman & J. J. Wurtman (Eds.). Nutrition and the brain. New York: Raven Press, vol. 7, pp. 139-166. Rosenthal, N. E., Sack, D. A. & Wehr, T. A. (1983). Seasonal variations in affective disorders. In T. A. Wehr & F. K. Goodwin (Eds.). Circadian rhythms inpsychiatry, Pacific Grove, CA: Boxwood Press. Rosenthal, N . E., Sack, D. A. & Gillin, J . C. (1984). Seasonal affective disorder: a description of the syndrome and preliminary findings with light therapy. Archives of General Psychiatry, 41, 72-80. Rosenthal, N. E., Carpenter, C. J . & James, S. P. (1985). Seasonal affective disorder in children and adolescents. American Journal of Psychiatry, 143, 356-358. Sandyk, R. (1991). Analgesic nitrous oxide in alcohol withdrawal: The role of melatonin. International Journal of Neuroscience, 56. 201-205. Satel, S. L. & Gawin, F. H. (1989). Seasonal cocaine abuse. American Journal of Psychiatry, 146, 534-535. Seguela, P., Geffard, M., Chauveau, J., Muyard, J. P., Biziere, K. & Le Moal, M. (1982). Selective increase of melatonin content in pineal gland and nuclcus accumbens after peripheral injection of des-Tyr'-gamma endorphin in the rat. Neuroscience Letters, 10, S442. Sevy, S . , Kay, S. R., Opler, L. A. & Van Praag, H. M. (1990). Significance of cocaine history in schizophrenia. The Journal of Nervous and Mental Disease, 178, 642-648. Shaw, K . M., Stem, G . M. & Sandler, M. (1973). Melatonin and parkinsonism. Lancet, I , 271-272. Terman, M. (1988). On the question of mechanism in phototherapy: considerations of clinical efficacy and epidemiology. Journal of Biological Rhythms, 3 , 155- 172. Thase, M. (1986). Defining and treating seasonal affective disorder. Psychiatric Annals, 16, 733-737. Thompson, C. & Isaacs, G. (1988). Seasonal affective disorder- a British sample. Journal of Affective Disorders, 14, 1-11.
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Touitou, Y., Bogdan, A., Claustrat, B. & Touitou, C . (1987). Drugs affecting melatonin secretion in man. In G. P. Trentini, C. De Gaetani & P. Pevet (Eds.). Fundamenrats and clinics in pineal research, vol. 44, New York: Raven Press, pp. 349-356. Wehr, T. A. & Rosenthal, N. E. (1989). Seasonality and affective illness. American Journal of Psychiatry, 146, 829-839. Winters, W. D., Alcaraz, M . , Cervantes, M. Y. & Flores-Guzman, C. (1973). The synergistic effect of reduced visual input on ketamine action- The possible role of the pineal gland. Neuropharmacology, 12, 407-416. Wurtman, J . J., Wurtman, R. J., Growdon, J. H., Henry, P., Lipscomb, A. & Zeisel, S. H . (1981). Carbohydrate craving in obese people: suppression by treatments affecting serotonergic transmission. International Journal of Eating Disorders, 1 , 2- 15. Yocca, F. D., DePaul Lynch, V. & Friedman, E. (1983). Effect of chronic lithium treatment on rat pineal rhythms: N-acetyltransferase, N-acetylserotonin and melatonin. Journal of Pharmacology and Experimental Therapeutics, 226, 733-137. Zatz, M. & Brownstein, M. J. (1979). Intraventricular carbachol mimics the effects of light on the circadian rhythm in the rat pineal gland. Science, 203, 358-361.
ISSN: 0020-7454 (Print) 1543-5245 (Online) Journal homepage: http://www.tandfonline.com/loi/ines20
Cocaine Addiction: Relationship to Seasonal Affective Disorder Reuven Sandyk & J. Daniel Kanofsky To cite this article: Reuven Sandyk & J. Daniel Kanofsky (1992) Cocaine Addiction: Relationship to Seasonal Affective Disorder, International Journal of Neuroscience, 64:1-4, 195-201, DOI: 10.3109/00207459209000545 To link to this article: http://dx.doi.org/10.3109/00207459209000545
Published online: 07 Jul 2009.
Submit your article to this journal
Article views: 8
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ines20 Download by: [137.189.171.235]
Date: 10 May 2016, At: 11:38
Infern. J . Neuroscience, 1992, Vol. 64, pp. 195-201 Reprints available directly from the publisher Photocopying permitted by license only
0 1992 Gordon and Breach Science Publishers S . A . Printed in the United States of America
ChicaZ Note COCAINE ADDICTION: RELATIONSHIP TO SEASONAL AFFECTIVE DISORDER REUVEN SANDYK and J . DANIEL KANOFSKY Department of Psychiatry, Albert Einstein College of Medicine/Montefore Medical Center, Bronx, New York, NY 10461, U.S.A.
Downloaded by [] at 11:38 10 May 2016
(Received December 20, 1990; in final form February 7 , 1992)
We report a 25 year-old patient with seasonal affective disorder (SAD) and cocaine abuse who experienced cyclical fluctuations in cocaine craving which were concomitant with seasonal alterations in mood. The temporal association of both disorders in this patient suggests that they may share a common underlying pathophysiology . Since disturbances in circadian rhythms and pineal melatonin functions may in part underlie the pathophysiology of SAD and the psychomimetic effects of cocaine are mediated in part through the pineal gland, we propose that dysfunction of circadian rhythms and pineal melatonin functions may partly mediate the association of SAD with cocaine abuse. This hypothesis may have potential clinical and therapeutic implications for a subgroup of cocaine abusers with SAD since light therapy, which is efficacious in the therapy of SAD, may also prove to be beneficial in reducing cocaine addiction. Furthermore, the report illustrates the need for investigations of environmental cues for cocaine abuse with specific attention given to the effects of light on circadian mood changes. Keywords: Cocaine use, pineal gland, seasonal affective disorder.
Epidemiological studies demonstrate that cocaine abuse has grown to epidemic proportions in the United States (Kay et al., 1990; Regier et al., 1990). This is especially true in the mentally ill. A recent epidemiologic study found that 20% of individuals with mental disorders also carry a current diagnosis of substance abuse disorder. Moreover, as many as 29% of all persons with mental disorders have a lifetime diagnosis of substance abuse disorder (Regier et al., 1990). For schizophrenia, the lifetime rate of substance dependence/abuse is 47% and for bipolar disorder, the rate increases to 56% (Regier et al., 1990). The latter findings suggest a causal or secondary relationship between substance abuse/dependence and the pathophysiology of affective disorders. Theories attempting to address the complex interaction between the abuse of psychoactive substances and psychopathology have commented on both substance abuse being the cause of psychiatric symptoms and use of drugs of abuse reflecting “selfmedication” for psychiatric symptoms (McLellan & Druley, 1977). For instance, the rewarding effect of cocaine is thought to be related to an increase in mesolimbic dopaminergic activity (Ellinwood & Gawin, 1988), which may explain its widespread use in patients with various psychiatric disorders associated with disturbances in central dopaminergic functions (Regier et al., 1990). Recent studies have linked the pathophysiology of affective disorders with disturbances in circadian rhythms and pineal melatonin functions (cf. Miles & Philbrick, Correspondence to: Prof. Reuven Sandyk, M.D., M.Sc. P.O. Box 203, Bedford Hills, NY, 10507, USA. 195
196
R. SANDYK AND J.D. KANOFSKY TABLE 1 Evidence Implicating the Pineal Gland in Substance Abuse Disorder
cocaine increases melatonin production the pineal gland mediates the effects of hallucinogenic psychomimetic drugs large amounts of melatonin are present in regions involved in reward mechanisms abnormal pineal functions occur in heroin addicts 5. lithium carbonate stimulates melatonin secretion and decreases cocaine craving 6. desipramine phase shifts melatonin secretion and attenuates cocaine craving 7 . melatonin reduces anxiety and produces feelings of contentment and general mood elevation
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1. 2. 3. 4.
1988). Melatonin secretion has been found to be reduced in bipolar affective disorder patients (Lewy et al., 1979). In addition, these patients demonstrate supersensitivity to light (Lewy et al., 1981). The effects of some antidepressant drugs in depressive illness may be related to their capacity to stimulate melatonin secretion (cf. Miles & Philbrick, 1988), while the efficacy of lithium carbonate in the prophylaxis of manic-depressive illness may be secondary to its ability to stimulate and/or phase delay melatonin secretion (Yocca et al., 1983; Touitou et al., 1987). Disturbances in melatonin secretion and functions may also underlie in part some of the symptoms of seasonal affective disorder (SAD) (Rosenthal et al., 1984; Rosenthal et al., 1986; Wehr & Rosenthal, 1989), a specific ‘biological’ subtype of affective illness (Thompson & Isaacs, 1988), which is characterised by seasonal patterns of depression during which time patients frequently experience an increased desire to sleep and increased appetite for carbohydrate rich foods during the autumn or winter months (Rosenthal et al., 1984; Wehr & Rosenthal, 1989). Since substance abuse is particularly common among patients with affective disorders, and since melatonin is implicated in the pathophysiology of at least some depressive illnesses, it is possible that disturbances in pineal melatonin functions may also underlie some substance abuse disorders. This notion is supported by the following observations (see Table 1): (a) cocaine and amphetamines increase melatonin production in rats (Backstrom & Wetterberg, 1973; Holtz et al., 1974), (b) the integrity of the pineal gland is necessary for the hallucinogenic manifestations of various hallucinogenic psychomimetic drugs such as LSD and mescaline (Winters et al., 1973), (c) relatively large amounts of immunoreactive melatonin are present in the nucleus accumbens (Seguela et al., 1982), a critical structure in the reward system (Bozarth, 1987), (d) abnormal pineal melatonin functions have been reported in heroin addicts (Esposti et al., 1986), (e) lithium carbonate, which stimulates and/ or phase shifts melatonin secretion in humans (Touitou et el., 1987), reportedly attenuates cocaine abuse in bipolar patients (Kleber & Gawin, 1984) and desipramine, which specifically attenuates cocaine craving (Gawin & Kleber, 1984; Satel & Gawin, 1989), phase shifts melatonin secretion in humans (Touitou et al., 1987), and (f) oral administration of melatonin reduces anxiety and produces feelings of contentment and general mood elevation (Anton-Tay et al., 1971; Shaw et al., 1973; Cramer et al., 1974). Although the precise role of the pineal gland in humans is largely elusive, there is evidence that it is involved in the regulation of circadian and seasonal variations of various biological functions. Involvement of the pineal gland in addictive behavior (cf. Sandyk, 1991) suggests that cocaine addiction may be influenced by seasonal changes. In fact, Rosenthal et al. (1983) reported cyclical “self-medication” with cocaine in patients with bipolar disorder and Satel and Gawin (1989) reported two patients with seasonal affective disorder in whom fluctuations in cocaine abuse par-
SEASONAL VARIATIONS IN COCAINE ABUSE
197
alleled the occurrence of seasonal dysphoria. In both patients cocaine abuse increased significantly during the fall and winter and declined spontaneously during the summer months. We present an additional patient with mild SAD in whom seasonal alterations in cocaine abuse paralleled spontaneous fluctuations in mood, sleep, appetite, and cognitive functions. We propose that in this patient the coexistence of SAD and cocaine abuse may have been mediated by a common underlying pathophysiological mechanism involving abnormal regulation of circadian rhythms and possibly associated with dysfunction of the pineal gland.
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CASE REPORT This 25 year-old single black man was admitted to the Bronx Psychiatric Center in New York City in October of 1989 with a diagnosis of substance abuse disorder and episodic cocaine-induced psychosis. His drug use dates back to 1978, when at the age of 13, he first began to use marijuana and phencyclidine (PCP). Since the age of 16 he had been using cocaine regularly and more recently, crack cocaine. The patient had normal developmental milestones and he was an average student in school. He dropped out of high school in the 10th grade as a result of excessive drug use which was associated with episodes of cocaine-related psychosis. Since then he had had multiple hospitalizations in numerous psychiatric facilities for cocaineinduced psychotic episodes and was treated with neuroleptic medication. In November of 1989 his addictive behavior worsened and his increased usage of crack cocaine had caused him to allegedly assault a woman on the subway and steal her gold chain. He was arrested and subsequently admitted to our institution under the provisions of CPL 730 Final Status. During his institutionalization he was treated with carbamazepine (800 mg/d) which attenuated his craving for cocaine. Unfortunately, the drug had to be discontinued owing to the development of first degree heart block which was judged to be secondary to carbamazepine. He is currently receiving no psychotrophic medication and random drug screens have found no evidence for cocaine use over the past year. A recent examination performed in mid-December of 1990 found him to be pleasant and cooperative. He was coherent, relevant, and oriented in the spheres of person, place, and time. His speech was normal in rate and rhythm. Hallucinations and delusions were denied. He admitted to “being a little sad” and staff members and the patient’s girlfriend commented that he was not as outgoing as usual. He denied suicidal or homocidal ideation; his affect was well modulated, and his judgment and insight were intact. A specific inquiry into his affect suggested that the patient may have suffered from mild SAD. Specifically, he reported experiencing distinct seasonal fluctuations in mood and other vegetative symptoms of depression since the age of 15 which preceded the use of cocaine; by mid-autumn and throughout the winter months he experienced hypersomnia, decreased concentration, loss of appetite, general apathy, decreased libido, lack of motivation, and inactivity. During the winter period he admitted to taking cocaine approximately 3-4 times per week and stated that he would have used cocaine even more frequently if it were financially possible. In contrast, with the onset of spring and during the summer months, he experienced elevation of mood, increased energy, improved concentration, decreased urge to sleep, increased libido, and increased appetite associated with weight gain of about 10 lb.
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He also reported a significant spontaneous decrease in cocaine craving and admitted to a cocaine use of once per week.
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DISCUSSION This case demonstrates an association between cocaine abuse and seasonal mood fluctuations in a patient with a mild form of SAD. The temporal relationship between cocaine abuse and seasonal changes in mood suggests that both disorders may share a common underlying pathophysiology. This notion is supported further by the observations that: (a) the dysphoric symptoms of SAD (Rosenthal et al., 1984) resemble those of cocaine withdrawal (Gawin & Ellinwood, 1988), (b) both appear to respond transiently to administration of cocaine (Satel & Gawin, 1989), and (c) both may be associated with dysregulation of dopaminergic reward and activation systems (Jacobsen et a]., 1987; Gawin & Ellinwood, 1988). The clinical criteria for SAD have been outlined by Rosenthal et al. (1984) and include: (a) a history of at least one episode of major depression as defined by the Research Diagnostic Criteria, (b) recurrent fall-winter depressions, at least two of which occurred during successive years, separated by nondepressed periods in spring and summer, (c) no other DSM-111 Axis I psychopathology, and (d) the absence of regularly occurring psychosocial variables that might account for the regular seasonal depressions. Although the above criteria are typical for SAD, many variations are seen and atypical forms of SAD may be more common than previously thought (Wehr & Rosenthal, 1989). A milder version of the condition has been reported to occur also in children and adolescents which also appears to respond to phototherapy (Rosenthal et al., 1985). The pathophysiology of SAD remains elusive. A recent report indicates that SAD is related to dysfunction deep in the right temporofrontal region (Hunt & Silverstone, 1990). According to the melatonin theory of SAD (Wehr & Rosenthal, 1989), which was inspired by animal studies of seasonal rhythms, changes in the length of the day trigger winter depression by modifying the pattern of nocturnal melatonin secretion, which acts as a chemical signal of darkness (Rosenthal et al., 1984). This hypothesis is supported in part by the findings of Lewy et al. (1987) revealing that the circadian rhythm phase in melatonin secretion is abnormally delayed in patients with winter depression. The circadian rhythm phase shijt hypothesis suggests that winter depression occurs when the circadian rhythm phases become abnormally delayed relative to sleep since dawn comes later (Wehr & Rosenthal, 1989). The circadian rhythm amplitude hypothesis suggests that winter depression is caused by a reduction in the amplitude of circadian rhythms and that light therapy attenuates winter depression by increasing the amplitude of circadian rhythms (Czeisler et al., 1987). An alternative possibility relates to the fact that since carbohydrate craving, an early and common feature of winter depression in patients with SAD, is linked to decreased serotonin (5-HT) metabolism (Wurtman et al., 1981), and since carbohydrate-rich diet increases brain 5-HT content (Femstrom & Wurtman, 1972), craving and other SAD symptoms are caused by a central 5-HT deficiency (Rosenthal & Heffernan, 1986). This hypothesis is consonant with the possibility that decreased melatonin functions may be related to winter depression in SAD since 5-HT is a precursor of melatonin. Moreover, since in experimental animals cocaine has been shown to increase melatonin secretion (Holtz et al., 1974), it is possible that in our patient cocaine abuse reflects a process of “self medication” aimed primarily at augmenting melatonin functions and therefore attenuating the winter depression in SAD.
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Thus, it is conceivable that the heightened abuse of cocaine during the winter time, when melatonin secretion is known to be reduced as a result of diminished light exposure, may reflect an endogenous mechanism aimed at increasing melatonin functions. However, the findings that bright light, which attenuates winter depression in patients with SAD (Wehr & Rosenthal, 1989), acutely inhibits human melatonin secretion (Lewy et al., 1980) argues against a direct relationship between decreased melatonin functions and winter depression in patients with SAD. Thus, clarification of the role of the pineal gland in SAD might shed further light on the relationships among SAD, cocaine abuse, and pineal melatonin functions. Light therapy is currently the most effective treatment for typical and atypical forms of SAD (Rosenthal et al., 1986; Lewy et al.. 1987; Wehr & Rosenthal, 1989). Since phototherapy is effective in the management of SAD, it is possible that it might also be effective in attenuating cocaine abuse in patients with SAD and its atypical forms. Moreover, since cholinergic drugs, such as carbachol, mimic the effects of light on the circadian rhythms in the rat pineal gland (Zatz & Brownstein, 1979), it is possible that drugs which increase cholinergic activity such as physostigmine and lecithin might attenuate cocaine abuse in patients with SAD, while agents with anticholinergic properties might exacerbate it. Recent epidemiological studies indicate that SAD is relatively common among patients with recurrent depression; prevalence rates of 16% to 38% have been cited in the literature (Thase, 1986; Garvey et al., 1988; Terman, 1988). In the general population, the prevalence of severe SAD is about 5% (cf. Wehr & Rosenthal, 1989). However, the incidence of mild SAD is significantly higher and it has been suggested that many individuals who neither meet criteria for major affective disorder nor seek treatment for their symptoms appear to experience mild SAD that interferes with their productivity and well being (cf. Wehr & Rosenthal, 1988). Given the high incidence of cocaine abuse in the general population, and particularly in patients with mental illness, it is conceivable that in a significant proportion of these patients, cocaine abuse may coexist with mild forms of SAD. Identification of these individuals could be important since light therapy may be a potentially effective modality in reducing cocaine abuse. Furthermore, the association between cocaine abuse with SAD indicates the need to develop investigations of environmental cues for cocaine addiction with special attention given to the effects of light on cyclical mood changes.
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