Marihuana Biological Effects (eBook)

Front Cover 1
Marihuana Biological Effects: Analysis, Metabolism, Cellular Responses, Reproduction and Brain 4
Copyright Page 5
Table of Contents 6
LIST OF PARTICIPANTS 12
FOREWORD 14
INTRODUCTION 
16 
LA MARIHUANA ET SES EFFETS SUR LA CELLULE 19
Part I: Quantification of Cannabinoids and Their Metabolites in Body Fluids and Tissues: Pharmacokinetics 22
CHAPTER 1. INTRODUCTION TO QUANTIFICATION OF 
24 
PHARMACOKINETICS AND METABOLISM 
25 
IMPORTANCE OF IDENTIFYING AND ASSAYING PLASMA LEVELS OF .1-THC OR URINARY 
26 
METHODOLOGY FOR ASSAYING .1-THC 26
GC-MS, 
28 
PLASMA LEVELS OF .1-THC AFTER SMOKING, I.V. AND ORAL ADMINISTRATION 
29 
SUMMARY 34
REFERENCES 34
CHAPTER 2. APPLICATIONS OF MASS SPECTROMETRY IN CANNABINOID RESEARCH 36
MATERIALS AND METHODS 38
EXTRACTION AND PURIFICATION PRIOR TO 
40 
GAS CHROMATOGRAPHY—MASS 
43 
RESULTS ANALYSIS OF 
43 
ANALYSIS OF 
44 
DISCUSSION 54
CHOICE OF INSTRUMENT 54
INTERNAL STANDARDS 54
METABOLIC AND PHARMACOKINETIC DATA 56
COMPARISON OF GLC—MS WITH OTHER PROCEDURES 57
OTHER GLC—MS EXPERIMENTS 57
ACKNOWLEDGEMENTS 63
REFERENCES 63
CHAPTER 3. IDENTIFICATION AND MEASUREMENT OF CANNABINOIDS AND THEIR IN VIVO METABOLITES IN LIVER BY GAS 
66 
INTRODUCTION 66
EXPERIMENTAL 67
COMPARISON OF DERIVATIVES FOR QUANTITATION 69
STUDIES ON TISSUE LEVELS OF METABOLITES 69
RESULTS AND DISCUSSION 70
QUANTITATION OF .1-THC 
78 
CONCLUSIONS 81
ACKNOWLEDGEMENTS 82
REFERENCES 82
CHAPTER 4. RELATION BETWEEN EFFECTS OF CANNABINOID DERIVATIVES ON THE TWITCH RESPONSE OF THE ISOLATED GUINEA-PIG ILEUM AND THEIR 
84 
EXPERIMENTAL 85
RESULTS AND DISCUSSION 85
SIDE-CHAIN HYDROXYLATED 
86 
OTHER CANNABINOIDS 88
SUMMARY 90
ACKNOWLEDGEMENTS 90
REFERENCES 90
CHAPTER 5. .7-TETRAHYDROCANNABINOL, A NON-PSYCHOTROPIC CANNABINOID: STRUCTURE-ACTIVITY CONSIDERATIONS 
92 
MATERIALS AND METHODS 93
EVALUATION OF 
98 
THE THC RECEPTOR CONCEPT 99
ACKNOWLEDGEMENT 101
REFERENCES 101
CHAPTER 6. THE RADIOIMMUNOASSAY OF CANNABINOIDS ITS CLINICAL, PHARMACOLOGICAL AND FORENSIC
102 
ANTIBODY PRODUCTION 102
ASSAY DEVELOPMENT 103
APPLICATIONS 105
REFERENCES 109
CHAPTER 7. DETERMINATION OF CANNABINOIDS IN URINE BY EMIT® HOMOGENEOUS ENZYME 
110 
INTRODUCTION 110
PREPARATION OF THE COMPONENTS 111
ASSAY PROTOCOL 113
SENSITIVITY/CROSSREACTIVITY 115
SENSITIVITY AND PRECISION 116
CLINICAL RESULTS 117
ACKNOWLEDGEMENTS 119
REFERENCES 119
CHAPTER 8. IN VITRO METABOLISM OF TETRAHYDROCANNABINOL BY RHESUS 
122 
CONCLUSION 123
ACKNOWLEDGEMENTS 124
REFERENCES 124
CHAPTER 9. PHARMACOKINETICS AND DISPOSITION OF .9-TETRAHYDROCANNABINOL AND ITS 
126 
ACKNOWLEDGEMENTS 141
REFERENCES 142
CHAPTER 10. SUMMARY OF SESSION 1 144
RÉSUMÉ 146
Part II: Cannabinoids and Cellular Metabolism 148
CHAPTER 11. INHIBITORY EFFECTS OF DELTA-9-TETRAHYDROCANNABINOL AND OTHER PSYCHOTROPIC DRUGS ON 
150 
MATERIALS AND METHODS 153
HARVESTING AND MEASUREMENT OF RADIOACTIVITY 153
PREPARATION OF THC AND OTHER 
154 
INTERACTION OF THC WITH PHA 154
FATE OF THC IN CULTURE 154
INTERACTIONS OF THC WITH SERUM OR CELLS 154
MEASUREMENTS OF GLUCOSE, LACTATE AND 
156 
RESULTS 
156 
FATE OF THC IN THE CULTURE 156
INTERACTIONS THC-ETHANOL 156
INTERACTION THC-PHA 157
INTERACTIONS THC-SERUM AND THC-CELLS 158
METABOLISM OF LYMPHOCYTES IN CULTURE 
159 
INHIBITION OF PRECURSOR UPTAKE BY THC 
160 
DISCUSSION 161
REFERENCES 164
CHAPTER 12. INHIBITION BY THC OF THYMIDINE TRANSPORT: 
166 
METHODS 167
RESULTS 169
DISCUSSION 174
ACKNOWLEDGEMENTS 179
REFERENCES 180
CHAPTER 13. EFFECT OF .9-TETRAHYDROCANNABINOL IN NUCLEOSIDE AND AMINO ACID UPTAKE IN REUBER H-35 
182 
INTRODUCTION 182
MATERIALS AND METHODS 183
RESULTS 184
DISCUSSION 188
ACKNOWLEDGEMENTS 190
REFERENCES 190
CHAPTER 14. CANNABINOIDS: THE INFLUENCE ON CELL PROLIFERATION AND MACROMOLECULAR 
192 
INTRODUCTION 192
I. INFLUENCE OF CANNABINOIDS ON 
193 
II. INFLUENCE OF CANNABINOIDS ON 
198 
III. INFLUENCE OF CANNABINOIDS ON THE GENOME 209
IV. CONCLUSION 227
ACKNOWLEDGEMENTS 227
REFERENCES 227
CHAPTER 15. DIFFERENCE IN RESPONSE TO VITAMIN C BETWEEN MARIHUANA AND TOBACCO 
230 
INTRODUCTION 230
MATERIAL AND METHODS 232
RESULTS 232
DISCUSSION 238
ACKNOWLEDGEMENT 239
REFERENCES 239
CHAPTER 16. MARIHUANA AND CELL FUNCTION 240
INTRODUCTION 240
MATERIALS AND METHODS 241
RESULTS 242
DISCUSSION 244
ACKNOWLEDGEMENT 248
REFERENCES 248
CHAPTER 17. EFFECT OF (–).9THC ON ATPase 
250 
INTRODUCTION 250
MATERIALS 251
RESULTS AND DISCUSSION 253
ACKNOWLEDGEMENTS 263
REFERENCES 263
CHAPTER 18. ( – )TRANS-.9-TETRAHYDROCANNABINOL: SYNAPTOSOMAL PHOSPHOLIPIDS, SYNAPTOSOMAL PLASMA MEMBRANE (Na+-K + )-ATPase, AND 
264 
SYNAPTOSOMAL PHOSPHOLIPIDS 267
DISCUSSION 268
ACKNOWLEDGEMENTS 269
REFERENCES 269
CHAPTER 19. BIOCHEMICAL ALTERATIONS INDUCED BY CANNABINOIDS IN THE LEYDIG CELLS OF THE RAT TESTIS IN VITRO: EFFECTS ON 
272 
METHODS 273
RESULTS 274
DISCUSSION 281
ACKNOWLEDGEMENTS 283
REFERENCES 284
CHAPTER 20. INFLUENCE OF DELTA-9-TETRAHYDROCANNABINOL ON CONTRACTION RATE AND ENZYMATIC 
286 
INTRODUCTION 286
MATERIALS AND METHODS 286
RESULTS 290
DISCUSSION 298
REFERENCES 298
CHAPTER 21. EFFECTS OF CANNABIS ON LUNGS 300
METHODS AND MATERIALS 302
RESULTS 305
DISCUSSION 314
ACKNOWLEDGEMENT 316
REFERENCES 316
CHAPTER 22. AN EXPERIMENTAL ANIMAL MODEL FOR QUANTIFYING THE BIOLOGIC EFFECTS OF MARIJUANA ON THE DEFENSE 
322 
INTRODUCTION 322
METHODS 323
RESULTS 335
DISCUSSION 344
ACKNOWLEDGEMENTS 347
REFERENCES 347
CHAPTER 23. CANNABINOIDS AND MEMBRANE-BOUND 
350 
INTRODUCTION 350
MATERIALS AND METHODS 351
RESULTS 354
DISCUSSION 359
CONCLUSIONS 361
ACKNOWLEDGEMENT 362
REFERENCES 362
CHAPTER 24. THE EFFECTS OF CANNABINOIDS ON RAT 
364 
INTRODUCTION 364
METHODS 365
RESULTS AND DISCUSSION 366
ACKNOWLEDGEMENT 369
REFERENCES 369
CHAPTER 25. THE EFFECT OF IN VIVO TREATMENT WITH ( – ).1- TETRAHYDROCANNABINOL, AND OTHER PSYCHOACTIVE DRUGS ON THE 
372 
INTRODUCTION 372
METHODS 373
RESULTS 374
DISCUSSION 377
ACKNOWLEDGEMENTS 379
REFERENCES 379
CHAPTER 26. LONG TERM EFFECTS OF DELTA-9- 
380 
INTRODUCTION AND HISTORY 380
LONG TERM OF ESTROGEN IN MICE 381
MATERIALS AND METHODS 382
RESULTS 382
THE EFFECT OF 
382 
THE EFFECT OF SESAME 
386 
THE EFFECT OF ESTROGEN, OF LIPIDS AND OF 
386 
THE EFFECT OF THC UPON CELLS OF 
387 
DISCUSSION 388
REFERENCES 390
CHAPTER 27. HYPOPLOID METAPHASES IN CULTURED 
392 
MATERIALS AND METHODS 393
RESULTS 394
DISCUSSION 395
ACKNOWLEDGEMENT 396
REFERENCES 396
CHAPTER 28. OBSERVATIONS IN CHRONIC HASHISH USERS: NUCLEAR ABERRATIONS IN BLOOD AND SPERM AND ABNORMAL 
398 
INTRODUCTION 398
MATERIAL AND METHODS 399
RESULTS AND DISCUSSION 399
CONCLUSION 407
ACKNOWLEDGEMENTS 407
REFERENCES 408
CHAPTER 29. CANNABINOIDS AND CELLULAR 
410 
1. ACTION AT THE LEVEL OF THE PLASMA MEMBRANE 410
2. HORMONAL INTERACTIONS AND EFFECTS 
410 
3. ACTION ON SPECIALIZED CELLS 410
Part III: Cannabis and Reproduction 414
CHAPTER 30. EFFECTS OF CANNABIS ON SEX HORMONES AND TESTICULAR ENZYMES 
416 
INTRODUCTION 416
METHODS 418
RESULTS 418
DISCUSSION 424
REFERENCES 425
CHAPTER 31. EFFECTS OF CANNABINOIDS ON 
428 
I. INTRODUCTION 428
II. SPERM MORPHOLOGY AND MUTAGENICITY 430
III. INFLUENCE OF CANNABINOIDS: 
430 
IV. CONCLUDING REMARKS 437
ACKNOWLEDGEMENT 438
REFERENCES 438
CHAPTER 32. EFFECTS OF MARIHUANA INHALATION 
440 
INTRODUCTION 440
MATERIALS AND METHODS 440
RESULTS 441
DISCUSSION 443
ACKNOWLEDGEMENT 448
REFERENCES 448
CHAPTER 33. CHANGES IN HUMAN SPERMATOZO 
450 
CLINICAL PROTOCOL 451
RESULTS 453
DISCUSSION 457
ACKNOWLEDGEMENT 459
REFERENCES 459
CHAPTER 34. EFFECTS OF CANNABINOIDS ON REPRODUCTIVE ORGANS IN THE 
462 
INTRODUCTION 462
MATERIALS AND METHODS 463
RESULTS 463
DISCUSSION 468
ACKNOWLEDGEMENTS 468
REFERENCES 468
CHAPTER 35. EFFECT OF .9-TETRAHYDROCANNABINOL (THC) ON FEMALE REPRODUCTIVE 
470 
INTRODUCTION 471
METHODS 471
RESULTS AND DISCUSSION 474
ACKNOWLEDGEMENTS 487
REFERENCES 487
CHAPTER 36. THE EFFECT OF A CRUDE MARIHUANA EXTRACT ON EMBRYONIC AND FOETAL 
490 
INTRODUCTION 490
METHOD 490
RESULTS AND DISCUSSION 492
SUMMARY 496
APPENDIX 496
ACKNOWLEDGEMENT 497
REFERENCES 497
CHAPTER 37. EFFECTS OF CANNABIS ON FETAL 
500 
INTRODUCTION 500
METHODS AND MATERIALS 503
RESULTS 507
DISCUSSION 515
ACKNOWLEDGEMENT 516
REFERENCES 516
CHAPTER 38. REPRODUCTION IN RHESUS MONKEYS CHRONICALLY EXPOSED TO 
522 
INTRODUCTION 522
METHODS 524
RESULTS 525
DISCUSSION 530
ACKNOWLEDGEMENT 532
REFERENCES 532
CHAPTER 39. CANNABIS AND REPRODUCTION: 
534 
TESTIS 534
OVARY 534
PRENATAL DEVELOPMENT 534
CLINICAL OBSERVATION 535
RÉSUMÉ 535
TESTICULE 535
OVAIRE 535
DEVELOPPEMENT PRENATAL 535
OBSERVATIONS CLINIQUES 536
Part IV: Cannabis and the Brain 538
CHAPTER 40. ULTRASTRUCTURAL AND BIOCHEMICAL 
540 
INTRODUCTION 540
DISCUSSION 549
ACKNOWLEDGEMENT 550
REFERENCES 550
CHAPTER 41. BRAIN BIOCHEMICAL ALTERATIONS IN NEONATES OF DAMS TREATED ORALLY WITH .9-TETRAHYDROCANNABINOL 
552 
INTRODUCTION 552
METHOD AND MATERIALS 553
EXPERIMENTAL DESIGN 553
RESULTS 554
DISCUSSION 556
ACKNOWLEDGEMENT 557
REFERENCES 557
CHAPTER 42. CANNABIS AND THE BRAIN WITH SPECIAL 
560 
CANNABIS-CLINICAL OBSERVATIONS 561
EXPERIMENTAL CONFIRMATION OF CLINICAL 
562 
CANNABINOIDS AND THE LIMBIC SYSTEM 568
BIOCHEMICAL MECHANISMS 578
REFERENCES 581
CHAPTER 43. CANNABIS AND BRAIN-STIMULATION 
588 
MATERIAL AND METHODS 589
RESULTS 591
DISCUSSION 599
REFERENCES 603
CHAPTER 44. CANNABIS AND THE DEVELOPMENT 
606 
TOLERANCE IN MAN 606
TOLERANCE IN ANIMALS TO VARIOUS 
607 
MECHANISM OF TOLERANCE 608
CROSS-TOLERANCE 608
CONCLUSIONS 609
REFERENCES 609
CHAPTER 45. PHARMACOLOGICAL SIMILARITIES AND 
612 
THC AND ANALGESIA 612
THC AND TOLERANCE 613
THC AND DEPENDENCE 616
DEPENDENCE IN LABORATORY ANIMALS 617
DEPENDENCE IN MAN 618
DEPENDENCE IN CANNABIS USERS 619
OTHER SIMILARITIES BETWEEN THC 
620 
INTERACTIONS BETWEEN THC AND MORPHINE 
620 
CONCLUSION 623
LITERATURE 624
CHAPTER 46. .9-TETRAHYDROCANNABINOL AND THE 
626 
METHODS 627
RESULTS 629
DISCUSSION 634
CONCLUSION 638
REFERENCES 638
CHAPTER 47. CANNABIS AND EPILEPSY 640
INTRODUCTION 640
METHODS 641
RESULTS 644
DISCUSSION 657
ACKNOWLEDGEMENT 660
REFERENCES 660
CHAPTER 48. MARIHUANA AND EPILEPSY: PARADOXICAL ANTICONVULSANT AND CONVULSANT 
664 
CRUDE MARIHUANA 665
CANNABIDIOL (CBD) 672
OTHER CANNABINOIDS 673
MECHANISMS 673
REFERENCES 676
CHAPTER 49. EFFECTS OF CANNABIS ON HUMAN EEG 680
REFERENCES 684
CHAPTER 50. EFFECTS OF MARIHUANA ON PAIN AND 
686 
INTRODUCTION TO SENSORY DECISION THEORY 686
INTRODUCTION TO PAIN STUDIES 689
INTRODUCTION TO MEMORY STUDIES 690
METHODS 691
RESULTS 693
MEMORY RESULTS 695
DISCUSSION 697
ACKNOWLEDGEMENT 699
REFERENCES 700
CHAPTER 51. RESIDUAL EFFECTS OF HIGH-DOSE 
702 
EXPERIMENTAL 703
DISCUSSION 709
REFERENCES 711
CHAPTER 52. SOCIAL BEHAVIOR OF RHESUS MONKEY 
714 
INTRODUCTION 714
METHODS 717
RESULTS 720
DISCUSSION 727
ACKNOWLEDGEMENT 731
REFERENCES 731
CHAPTER 53. CHRONIC MARIHUANA SMOKING: ITS EFFECT ON FUNCTION AND 
734 
NONSPECIFIC EFFECTS OF SMOKE 735
DOSE LEVELS 735
MODIFIED SMOKING APPARATUS 737
OTHER CANNABIS DERIVATIVES 738
ELECTRON MICROSCOPIC STUDIES 740
REFERENCES 751
CHAPTER 54. CANNABIS AND THE BRAIN: A SUMMARY 752
CATECHOLAMINES 752
ELECTROPHYSIOLOGICAL AND NEUROANATOMICAL 
752 
BEHAVIORAL EFFECTS 752
TOLERANCE 
753 
EFFECTS IN EPILEPSY 753
EFFECTS ON HUMAN EEG AND MEMORY 753
RESUMÉ 753
CATECHOLAMINES 754
ELECTROPHYSIOLOGIE ET NEUROANATOMIE 754
COMPORTEMENT 754
TOLERANCE ET SYNDROME D'ABSTINENCE 754
ACTION DANS L'EPILEPSIE 754
ACTION SUR L'EEG ET LA MEMOIRE CHEZ 
755 
CONCLUDING SUMMARY 756
APPENDIX CANNABIS AND ALCOHOL: 
760 
AUTHOR INDEX 768
SUBJECT INDEX 790