ثنائي إيثيل أميد حمض الليسرجيك

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ثنائي إيثيل أميد حمض الليسرجيك (LSD)
INN : ليسرجيد
Lysergsäurediethylamid (LSD).svg
الصيغة الهيكلية ثنائية الأبعاد لـ LSD
Lsd3D.gif
نموذج ثلاثي الأبعاد لـ LSD
بيانات سريرية
النطق/ daɪ eθəl æmaɪd / ، / æmɪd / ، or / eɪmaɪd / [1] [2] [3]
اسماء اخرىLSD ، LSD-25 ، حمض ، Delysid ، أخرى
AHFS / Drugs.comالمرجعي

مسؤولية التبعية		منخفض [4]

مسؤولية الإدمان		نادرة منخفضة [5]
طرق
الإدارة		عن طريق الفم ، تحت اللسان ، في الوريد
فئة المخدراتمهلوس ( مخدر )
كود ATC
  • لا أحد
الوضع القانوني
الوضع القانوني
بيانات حركية الدواء
التوافر البيولوجي71٪ [6]
ارتباط البروتينغير معروف [7]
الأيضالكبد ( CYP450 ) [6]
المستقلبات2-Oxo-3-hydroxy-LSD [6]
بداية الحدث30-40 دقيقة [8]
نصف العمر القضاء3.6 ساعة [6] [9]
مدة العمل8-20 ساعة [10]
إفرازالكلى [6] [9]
معرفات
  • (6aR,9R)-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide
CAS رقم
PubChem إدارة البحث الجنائي
IUPHAR / BPS
DrugBank
كيم سبايدر
UNII
تشيبي
شيمبل
PDB يجند
لوحة معلومات CompTox ( EPA )
ECHA InfoCard100.000.031 Edit this at Wikidata
البيانات الكيميائية والفيزيائية
معادلةج 20 H 25 N 3 O
الكتلة المولية323.440  جم · مول -1
نموذج ثلاثي الأبعاد ( JSmol )
نقطة الانصهار80 إلى 85 درجة مئوية (176 إلى 185 درجة فهرنهايت)
  • InChI=1S/C20H25N3O/c1-4-23(5-2)20(24)14-9-16-15-7-6-8-17-19(15)13(11-21-17)10-18(16)22(3)12-14/h6-9,11,14,18,21H,4-5,10,12H2,1-3H3/t14-,18-/m1/s1 checkY
  • Key:VAYOSLLFUXYJDT-RDTXWAMCSA-N checkY
  (تحقق)

ثنائي إيثيل أميد حمض الليسرجيك ( LSD ) ، [أ] المعروف أيضًا بالعامية باسم حمض ، هو دواء مخدر . [11] تشتمل التأثيرات عادةً على تكثيف الأفكار والعواطف والإدراك الحسي. [12] في جرعات عالية بما فيه الكفاية كشوف LSD البصرية في المقام الأول، وكذلك السمع، الهلوسة . [13] [14] من الأمور النموذجية اتساع حدقة العين وزيادة ضغط الدم وزيادة درجة حرارة الجسم. [15] بما أن عقار إل إس دي يرتبط بمستقبلات الدوبامين بالإضافة إلى مستقبلات السيروتونينكما أن تأثيراته أكثر نشاطًا وسرعة مقارنة بالمخدرات مثل psilocybin ، وهو ليس منبهات الدوبامين . [16] تبدأ التأثيرات عادةً في غضون نصف ساعة ويمكن أن تستمر لمدة تصل إلى 20 ساعة. [15] [17] LSD هي أيضا قادرة على التسبيب خبرات صوفية و حل الأنا ، وإن كان أقل كثيرا من مركبات مثل سيلوسيبين. [18] [14] يتم استخدامه بشكل أساسي كدواء ترفيهي أو لأسباب روحية . [15] [19]LSD هو مخدر نموذجي وواحد من المخدر "الكلاسيكي" ، كونه مخدر ذو أهمية علمية وثقافية كبيرة. [11]

يعتبر عقار إل إس دي غير مسبب للإدمان مع احتمالية منخفضة للتعاطي. [20] [21] لا توجد محاولات مسجلة ناجحة لتدريب الحيوانات على إعطاء عقار إل إس دي ذاتيًا في البيئات المختبرية. [21] الاستخدام المتكرر يبني التسامح بسرعة ، ويتطلب جرعات أكبر بشكل مضاعف للشعور بالتأثير. ردود الفعل النفسية السلبية الممكنة، مثل القلق ، جنون العظمة ، و الأوهام . [7] من الممكن أن يتسبب عقار إل إس دي في إحداث هلوسات بصرية متقطعة أو مزمنة ، على الرغم من عدم استخدامها مرة أخرى ، في بعض الأفراد ، عادةً في غياب التأثيرات النفسية المرتبطة بـ LSD. وتشمل الآثار المشتركة الثلوج البصرية و تكرر المرئي. في الحالات التي يسبب فيها ذلك ضائقة أو ضعفًا ، يتم تشخيصه على أنه اضطراب الإدراك المستمر المهلوس (HPPD). [22] [23] في حين أن الجرعة الزائدة من عقار إل إس دي غير معروفة ، على الرغم من وجود دراسات حالة مختلفة للأفراد الذين يتناولون جرعات عالية للغاية ، [11] يمكن أن يسبب LSD الإصابة والوفاة نتيجة للحوادث الناجمة عن ضعف نفسي. [15] [11] يُعتقد أن تأثيرات LSD تنبع أساسًا من كونها ناهض في مستقبلات 5-HT 2A . [21] [7] [11] بينما لا تزال الطبيعة الدقيقة لكيفية تأثير عقار إل إس دي لتأثيراته عبر هذا المستقبل غير معروفة ،نشاط شبكة الوضع الافتراضي الذي يسبب زيادة مقابلة في التوصيل الوظيفي العالمي ، [24] [25] [26] بالإضافة إلى زيادة انتقال الجلوتامات ، [11] من المحتمل أن تكون الآليات الأساسية الأساسية. LSD قوي بشكل استثنائي ، مع أقل من 20 ميكروغرام قادرة على إحداث تأثير ملحوظ. [15] في شكله النقي ، يكون عقار إل إس دي واضحًا أو أبيض اللون ، وليس له رائحة ، وهو بلوري . [12] يتحلل مع التعرض للأشعة فوق البنفسجية . [15]

اعتبارًا من عام 2017 ، استخدم حوالي 10٪ من الأشخاص في الولايات المتحدة عقار إل إس دي في مرحلة ما من حياتهم ، بينما استخدمه 0.7٪ في العام الماضي. [27] كان الأكثر شيوعًا في الستينيات إلى الثمانينيات. [15] زاد استخدام عقار إل إس دي بين البالغين في الولايات المتحدة بنسبة 56.4٪ من عام 2015 إلى عام 2018. [28] عادةً ما يتم ابتلاع عقار إل إس دي أو وضعه تحت اللسان. [12] غالبًا ما يباع على ورق نشاف وأقل شيوعًا على شكل أقراص أو مربعات جيلاتينية . [15]

تم تصنيعه لأول مرة من قبل الصيدلي LSD السويسري ألبرت هوفمان في عام 1938 من حمض الليسرجيك ، وهي مادة كيميائية مشتقة من التحلل من الإرغوتامين ، وهو قلويد وجدت في الشقران ، نوع من الفطريات التي تصيب الشعير في المقام الأول بين الحبوب الأخرى. [15] [22] LSD كانت واحدة من lysergamides هوفمان التي تم تصنيعها من حمض الليسرجيك أثناء العمل في Sandoz في بازل ، سويسرا أثناء محاولة تطوير منبه تنفسي جديد. اكتشف هوفمان آثاره على البشر في عام 1943 ، بعد تناوله للمادة عن غير قصد ، وربما يمتصها من خلال جلده. [29] [30] [31] كان عقار إل إس دي موضع اهتمام استثنائي في مجال الطب النفسي في الخمسينيات وأوائل الستينيات من القرن الماضي ، مع قيام ساندوز بتوزيع عقار إل إس دي على الباحثين تحت اسم العلامة التجارية ديليسيد في محاولة لإيجاد استخدام قابل للتسويق له. [30]

كان يُعتقد في البداية أن عقار إل إس دي يحاكي مرض انفصام الشخصية ، حيث يتم تصنيفه على أنه " مقلد نفسي " ، ونتيجة لذلك كان يُنظر إليه على أنه أداة لفهم أفضل لكيفية تغيير الفصام للإدراك ذاتيًا. حقيقة أن الدوبامين و مسكالين متشابهة كيميائيا - منذ كلاهما phenethylamines - جنبا إلى جنب مع قوة عالية من LSD أدى أيضا إلى النظرية القائلة بأن الفصام سببه مادة مهلوسة تنتج التطور الطبيعي بكميات صغيرة بما يكفي لتبقى غير مكتشفة. [30]ومع ذلك ، تم التخلي عن نموذج المحاكاة النفسية في نهاية المطاف بسبب قدرته المُبلغ عنها على إحداث تجارب متعالية ذات فائدة نفسية دائمة - على عكس الفصام. كان الاستخدام الطبي لهذه الخاصية رائدًا في شكل العلاج النفسي بمساعدة LSD من قبل الأطباء النفسيين مثل همفري أوزموند ، مع نتائج واعدة في مجالات مثل إدمان الكحول ، [32] [30] [33] [34] مما أدى إلى صياغة أوزموند للمصطلح "مخدر" ( إظهار العقل المضاء ) كمصطلح لـ LSD و mescaline ليحل محل "المقلد النفسي". خلال هذا الوقت ، وكالة المخابرات المركزية(CIA) كانت مهتمة بـ LSD كإضافة إلى أبحاثها الموجودة مسبقًا في استخدام المواد ذات التأثير النفساني للمساعدة في الاستجواب في إطار مشروع MKUltra ، على الرغم من أن وكالة المخابرات المركزية أوقفت في النهاية البحث في هذا لصالح إمكانية إعطاء LSD لقادة العالم حتى يشوهوا مصداقيتهم. تحت تأثيرها ، مما أدى إلى قيام وكالة المخابرات المركزية بإدارة عقار إل إس دي لأشخاص خضعوا للاختبار عن غير قصد من أجل مراقبة رد فعلهم ، ومن أشهر الأمثلة على ذلك عملية ذروة منتصف الليل . [30] كان عقار إل إس دي أحد المواد ذات التأثير النفساني العديدة التي تم تقييمها من قبل الفيلق الكيميائي للجيش الأمريكي على أنها مواد غير قاتلة محتملة في Edgewood Arsenalفي ولاية ماريلاند . أجريت بعض هذه الاختبارات أيضًا على البشر. [30]

في الستينيات من القرن الماضي ، تم تبني LSD والمخدرات الأخرى من قبل حركة الثقافة المضادة وأصبحت مرادفة لها نظرًا لقدرتها المتصورة على `` توسيع الوعي '' ، مما أدى إلى اعتبار LSD تهديدًا ثقافيًا للقيم الأمريكية وجهود حرب فيتنام وتصنيفها كمواد من مواد الجدول الأول في عام 1968. [35] تم إدراجه كمواد خاضعة للرقابة في الجدول 1 من قبل الأمم المتحدة في عام 1971 [15] وليس له حاليًا استخدامات طبية معتمدة. [15] في نوفمبر 2020 ، قرر استفتاء أنه سيتم إلغاء تجريمه في ولاية أوريغون الأمريكية .[36]

الاستخدامات

ترفيهية

يشيع استخدام عقار إل إس دي كدواء ترفيهي بصحبة الأصدقاء أو في حشود كبيرة أو من قبل الشخص نفسه. [37]

روحي

يمكن أن تحفز LSD التجارب الروحية الشديدة وبالتالي تعتبر entheogen . أبلغ بعض المستخدمين عن تجارب خارج الجسم . في عام 1966 ، أسس تيموثي ليري رابطة الاكتشاف الروحي مع إل إس دي كسر مقدس لها . [38] [39] ستانيسلاف جروف وقد كتب أن التجارب الدينية والصوفية لوحظ خلال جلسات LSD يبدو أن phenomenologically تمييزه عن أوصاف مماثلة في الكتب المقدسة للديانات الكبرى في العالم ونصوص القديمة الحضارات . [40]

طبي

ليس لـ LSD حاليًا أي استخدامات معتمدة في الطب . [41] [42] و تحليل ميتا خلص إلى أن جرعة واحدة كانت فعالة في الحد من استهلاك الكحول في إدمان الكحول . [43] تمت دراسة LSD أيضًا في حالات الاكتئاب والقلق والاعتماد على المخدرات ، مع نتائج أولية إيجابية. [44]

تأثيرات

تم الإبلاغ عن بعض أعراض LSD [45] [46]

بدني

يمكن أن يسبب LSD اتساع حدقة العين ، وانخفاض الشهية ، والتعرق الغزير ، واليقظة. ردود الفعل الجسدية الأخرى على LSD متغيرة للغاية وغير محددة ، وبعضها قد يكون ثانويًا للتأثيرات النفسية لـ LSD. من بين الأعراض المبلغ عنها ارتفاع درجة حرارة الجسم ، وسكر الدم ، ومعدل ضربات القلب ، إلى جانب قشعريرة ، صرير في الفك ، وجفاف في الفم ، وفرط المنعكسات . في التجارب السلبية ، تم أيضًا عرض الخدر والضعف والغثيان والرعشة. [15]

نفسي

معظم الآثار النفسية المباشرة المشتركة للLSD و الهلوسة البصرية و أوهام (المعروف شعبيا باسم " رحلات ")، والتي تختلف تبعا لمدى يستخدم وكيف يتفاعل الدواء مع الدماغ. تبدأ الرحلات عادة في غضون 20-30 دقيقة من تناول عقار إل إس دي عن طريق الفم (أقل إذا تم استنشاقها أو أخذها عن طريق الوريد) ، وتبلغ ذروتها من ثلاث إلى أربع ساعات بعد الابتلاع ، ويمكن أن تستمر حتى 20 ساعة في الجرعات العالية. قد يعاني المستخدمون أيضًا من "توهج" من المزاج المحسن أو الحالة العقلية المتصورة لأيام أو حتى أسابيع بعد تناول بعض التجارب. [47]يقال إن الرحلات الجيدة محفزة وممتعة للغاية ، وعادة ما تنطوي على فرح شديد أو نشوة ، وتقدير أكبر للحياة ، وتقليل القلق ، وإحساس بالتنوير الروحي ، وشعور بالانتماء أو الترابط مع الكون. [48] [49] التجارب السلبية ، المعروفة بالعامية باسم "الرحلات السيئة" ، تثير مجموعة من المشاعر المظلمة ، مثل الخوف غير المنطقي والقلق والذعر والبارانويا والرهبة وعدم الثقة واليأس وحتى التفكير الانتحاري . [50] في حين أنه من المستحيل التنبؤ بموعد حدوث رحلة سيئة ، يمكن التحكم في الحالة المزاجية للشخص ومحيطه ونومه وترطيبه ووضعه الاجتماعي وعوامل أخرى (يشار إليها بالعامية باسم " الإعداد والإعداد ") لتقليل مخاطر رحلة سيئة.[51] [52]

حسي

يسبب LSD و الرسوم المتحركة التجربة الحسية من الحواس ، العواطف ، ذكريات ، والوقت، و الوعي لمدة 6 إلى 20 ساعة، وهذا يتوقف على الجرعة والتسامح. [17] بشكل عام يبدأ في غضون 30 إلى 90 دقيقة بعد الابتلاع ، قد يواجه المستخدم أي شيء من التغييرات الطفيفة في الإدراك إلى التحولات المعرفية الساحقة . التغييرات في الإدراك السمعي والبصري هي أيضا نموذجية. [53] [54]

قد تتضمن بعض التأثيرات الحسية تجربة ألوان مشعة أو أكثر حيوية ، وأشياء وأسطح تبدو وكأنها تموج ، أو "تتنفس" ، أو تتحرك بطريقة أخرى ، وفركتلات دوارة متراكبة على رؤية المرء ، وأنماط ملونة خلف الجفون المغلقة ، وإحساس متغير بالوقت ، وأنماط هندسية الناشئة على الجدران وغيرها من الأشياء المنسوجة ، وتحويل الأشياء. [53] أبلغ بعض المستخدمين أيضًا عن طعم معدني قوي طوال مدة التأثيرات. [٥٥] قد يختلف قوام الطعام أو مذاقه ، وقد ينفر المستخدمون أيضًا من الأطعمة التي يستمتعون بها عادةً. تم العثور على تأثيرات مماثلة في الفئران. [56]

يقول البعض أن عالم الجماد يبدو وكأنه يتحرك بطريقة يتعذر تفسيرها ؛ على سبيل المثال ، يمكن أن تبدو الكائنات الثابتة في ثلاثة أبعاد وكأنها تتحرك بالنسبة إلى واحد أو أكثر من الأبعاد المكانية الإضافية. [57] العديد من التأثيرات البصرية الأساسية تشبه الفوسفين الذي شوهد بعد الضغط على العين وقد تمت دراستها أيضًا باعتبارها ثوابت الشكل . في بعض الأحيان يمكن تغيير هذه التأثيرات والأنماط عند التركيز عليها ، أو يمكن تغييرها بناءً على الأفكار أو العواطف أو الموسيقى. [58] قد تشمل التأثيرات السمعية لعقار LSD صدى- مثل تشوهات الأصوات ، والتغيرات في القدرة على تمييز المحفزات السمعية والبصرية المتزامنة ، والتكثيف العام لتجربة الموسيقى. غالبًا ما تسبب الجرعات العالية تشوهات شديدة وأساسية في الإدراك الحسي مثل الحس المواكب ، وتجربة أبعاد مكانية أو زمنية إضافية ، وانفصال مؤقت .

الآثار السلبية

خبراء الإدمان في الطب النفسي والكيمياء والصيدلة وعلم الطب الشرعي وعلم الأوبئة والشرطة والخدمات القانونية المشاركة في تحليل دلفي فيما يتعلق بـ 20 عقارًا ترفيهيًا شائعًا. احتلت LSD المرتبة 14 في الاعتماد ، والمرتبة 15 في الأذى الجسدي ، والمرتبة 13 في الضرر الاجتماعي. [59]

من بين 20 عقارًا تم تصنيفها حسب ترتيب الضرر الفردي والمجتمعي بواسطة David Nutt ، احتل LSD المرتبة الثالثة في المرتبة الأخيرة ، أو ما يقرب من 1/10 على أنها ضارة مثل الكحول. كان التأثير الضار الأكثر أهمية لـ LSD هو ضعف الأداء العقلي أثناء التسمم. [60]

اختلالات عقلية

قد يثير عقار إل إس دي نوبات هلع أو مشاعر القلق الشديد ، والمعروفة بالعامية باسم " رحلة سيئة ". LSD قادر على تفاقم الأمراض العقلية والتعجيل بالظهور المبكر لمرض انفصام الشخصية لدى الأفراد المعرضين للخطر. [11] على الرغم من أن الدراسات السكانية لم تجد زيادة في حالات الإصابة بالأمراض العقلية لدى متعاطي المخدرات المخدرة بشكل عام ، مع وجود معدلات اكتئاب وتعاطي مواد مخدرة أقل من مستخدمي المواد المخدرة مقارنةً بالمجموعة الضابطة ، [61] [62] هناك دليل على أن الأشخاص المصابين الأمراض العقلية الحادة مثل الفصام لديها احتمالية أكبر للتعرض لآثار سلبية من تناول عقار إل إس دي. [63]

الإيحاء

بينما تشير الوثائق المتاحة علنا بأن وكالة المخابرات المركزية و وزارة الدفاع قد توقف البحث في استخدام LSD كوسيلة لل سيطرة على العقل ، [64] بحوث من 1960s تشير إلى أن كلا من الناس المصابين بأمراض عقلية وصحية أكثر إيحاء حين تحت نفوذها. [65] [66] [67]

ذكريات الماضي

" ذكريات الماضي " هي ظاهرة نفسية تم الإبلاغ عنها حيث يعاني الفرد من حلقة من بعض التأثيرات الذاتية لعقار إل إس دي بعد زوال العقار ، وتستمر لأشهر أو سنوات بعد تعاطي الهلوسة . [68] يعاني الأفراد المصابون باضطراب الإدراك المستمر من الهلوسة من استرجاع الأحداث المتقطعة أو المزمنة التي تسبب الضيق أو الضعف في الحياة والعمل. [23]

السرطان والحمل

و مطفرة إمكانات LSD غير واضحة. بشكل عام ، يبدو أن الأدلة تشير إلى تأثير محدود أو معدوم على الجرعات شائعة الاستخدام. [69] لم تظهر الدراسات أي دليل على تأثيرات ماسخة أو مطفرة. [7]

الإدمان والتسامح

التسامح لLSD يتراكم مع الاستخدام المستمر [70] و عبر التسامح وقد تجلى بين LSD، الميسكالين ، [71] و سيلوسيبين . [72] يعتقد الباحثون أن التسامح يعود إلى خط الأساس بعد أسبوعين من عدم استخدام المخدر. [73]

و NIH تنص على أن LSD هو الادمان، [22] بينما تنص معظم مصادر أخرى ليست كذلك. [20] [74] ينص كتاب مدرسي عام 2009 على أنه "نادرًا ما ينتج عنه استخدام قهري." [5] تشير مراجعة عام 2006 إلى أنه يتم إساءة استخدامها بسهولة ، ولكنها لا تؤدي إلى الإدمان. [20] لا توجد محاولات ناجحة مسجلة لتدريب الحيوانات على إعطاء عقار إل إس دي ذاتيًا في البيئات المختبرية. [21]

جرعة مفرطة

ذكر تقرير في عام 2008 أنه على الرغم من عدم وجود "مراجعة شاملة منذ الخمسينيات" و "عدم وجود بحث سريري قانوني تقريبًا" منذ السبعينيات ، لم يكن هناك "وفيات بشرية موثقة بسبب جرعة زائدة من عقار إل إس دي". ثمانية أفراد استهلكوا عن طريق الخطأ كميات كبيرة جدًا عن طريق الخلط بين عقار إل إس دي والكوكايين أصيبوا بحالة غيبوبة ، وارتفاع الحرارة ، والقيء ، ونزيف المعدة ، ومشاكل في الجهاز التنفسي - جميعهم نجوا برعاية داعمة. [7] وفقًا لتقارير أكثر حداثة ، حدثت العديد من حالات الوفاة وحالات الانتحار المرتبطة بالسلوك بسبب عقار إل إس دي. [75] [76] الطمأنينة في بيئة هادئة وآمنة مفيدة. يمكن معالجة التهيج بأمان باستخدام البنزوديازيبينات مثل لورازيبام أو الديازيبام. لا ينصح باستخدام مضادات الذهان مثل هالوبيريدول لأنها قد تكون لها آثار ضارة. يتم امتصاص عقار إل إس دي سريعًا ، لذا فإن الفحم النشط وإفراغ المعدة ليس لهما فائدة تذكر ، ما لم يتم ذلك في غضون 30-60 دقيقة من تناول جرعة زائدة من عقار إل إس دي. نادرًا ما تكون هناك حاجة للتخدير أو التقييد الجسدي ، وقد يتسبب التقييد المفرط في حدوث مضاعفات مثل ارتفاع الحرارة ( ارتفاع درجة الحرارة ) أو انحلال الربيدات . [77]

يجب معالجة الجرعات الكبيرة "برعاية داعمة ، بما في ذلك الدعم التنفسي والتنبيب الرغامي إذا لزم الأمر. يجب معالجة ارتفاع ضغط الدم [ارتفاع ضغط الدم] وعدم انتظام دقات القلب [تسارع ضربات القلب] وارتفاع الحرارة بأعراض. ​​يجب معالجة انخفاض ضغط الدم [انخفاض ضغط الدم] في البداية بالسوائل ثم بالضواغط إذا لزم الأمر ". "الوريد من مضادات التخثر ، موسعات ، و sympatholytics قد يكون مفيدا" عند علاج التسمم الأرغوني . [77]

علم العقاقير

الديناميكا الدوائية

الصلات الملزمة لـ LSD لمستقبلات مختلفة. كلما انخفض ثابت التفكك (K i ) ، زادت قوة ارتباط LSD بهذا المستقبل (أي مع تقارب أعلى). يمثل الخط الأفقي قيمة تقريبية لتركيزات البلازما البشرية لـ LSD ، وبالتالي ، من غير المحتمل أن تشارك تقاربات المستقبلات الموجودة فوق الخط في تأثير LSD. متوسط ​​البيانات من البيانات من قاعدة بيانات K i

معظم مخدر هرمون السيروتونين ليس للدوبامين بشكل كبير ، وبالتالي فإن LSD غير نمطية في هذا الصدد. قد يساهم نبه مستقبل D 2 بواسطة LSD في آثاره النفسانية التأثير على البشر. [78] [79]

يربط LSD لمعظم أنواع فرعية مستقبلات السيروتونين باستثناء -HT 5 3 و 5-HT 4 مستقبلات . ومع ذلك ، تتأثر معظم هذه المستقبلات عند التقارب المنخفض جدًا ليتم تنشيطها بشكل كافٍ بواسطة تركيز الدماغ الذي يبلغ حوالي 10-20  نانومتر . [74] في البشر ، يمكن أن تؤثر الجرعات الترفيهية من LSD على 5-HT 1A (K i = 1.1 نانومتر) ، 5-HT 2A (K i = 2.9 نانومتر) ، 5-HT 2B (K i = 4.9 نانومتر) ، 5- HT 2C (K i = 23 نانومتر) ، 5-HT 5A (K i= 9 نانومتر [في أنسجة الفئران المستنسخة]) ، ومستقبلات 5-HT 6 (K i = 2.3 نانومتر). [80] [81] على الرغم من عدم وجودها في البشر ، فإن مستقبلات 5-HT 5B الموجودة في القوارض لها أيضًا تقارب كبير مع LSD. [82] تُعزى التأثيرات المخدرة لـ LSD إلى التنشيط المتقاطع لمغاير مستقبلات 5-HT 2A . [83] كثير ولكن ليس كل 5-HT 2A منبهات هي المنشطات و5-HT 2A الخصوم عرقلة النشاط مخدر من عقاقير الهلوسة. يعرض LSD الانتقائية الوظيفية في مستقبلات 5-HT 2A و 5HT 2C حيث أنه ينشط إنزيم تحويل الإشارة phospholipase A2 بدلاً من تنشيط إنزيم phospholipase C كما يفعل يجند السيروتونين الداخلي. [84]

بالضبط كيف تنتج LSD آثاره غير معروف، ولكن يعتقد أنه يعمل عن طريق زيادة الغلوتامات الافراج عنه في قشرة الدماغ [74] وبالتالي إثارة في هذا المجال، وتحديدا في طبقات الرابع والخامس. [85] LSD، مثل العديد من الأدوية الأخرى من الاستخدام الترفيهي ، فقد ثبت أنه ينشط المسارات ذات الصلة بـ DARPP-32 . [86] ويعزز المخدرات الدوبامين D 2 مستقبلات protomer الاعتراف و يشير من D 2 -5-HT 2A المجمعات مستقبل، [87] التي قد تسهم في آثاره النفسية. [87]لقد ثبت أن LSD لها تقارب منخفض لمستقبلات H1 ، مما يعرض تأثيرات مضادات الهيستامين. [88] [89] [90]

LSD هو ناهض متحيز يحث على التشكل في مستقبلات السيروتونين التي تفضيل تجنيد بيتا-أوقفين على تنشيط بروتينات جي . [91] [92] لديها LSD أيضا طويلة بشكل استثنائي وقت الإقامة عند منضمة إلى مستقبلات السيروتونين ساعات دائم، بما يتفق مع تأثيرات طويلة الأمد من LSD على الرغم السريع نسبيا التخليص . [91] [92] يكشف التركيب البلوري المكون من 5-HT 2B المرتبط بـ LSD عن حلقة خارج الخلية تشكل غطاءً فوق نهاية ثنائي إيثيلاميد من تجويف الربط وهو ما يفسر المعدل البطيء لفك ارتباط LSD من مستقبلات السيروتونين. [93] [94] [95]إن حمض ليسرجاميد ليسرجيك أميد (LSA) ذي الصلة الذي يفتقر إلى جزء ثنائي إيثيلاميد هو أقل بكثير من الهلوسة بالمقارنة. [95]

الدوائية

تستمر آثار LSD عادة ما بين 6 و 12 ساعة حسب الجرعة والتسامح ووزن الجسم والعمر. [96] حذرت نشرة Sandoz الخاصة بـ "Delysid": "الاضطرابات المتقطعة في التأثير قد تستمر أحيانًا لعدة أيام". [97] وجد Aghajanian و Bing (1964) أن LSD لها نصف عمر للتخلص منها 175 دقيقة فقط (حوالي 3 ساعات). [80] ومع ذلك ، باستخدام تقنيات أكثر دقة ، أفاد Papac and Foltz (1990) أن 1 ميكروغرام / كغ عن طريق الفم LSD يعطى لمتطوع واحد من الذكور لديه نصف عمر واضح للبلازما يبلغ 5.1 ساعة ، مع ذروة تركيز البلازما من 5 نانوغرام / مل في 3 ساعات بعد الجرعة. [98]

و الدوائية لم يحدد من LSD بشكل صحيح حتى عام 2015، والتي ليس من المستغرب لدواء مع هذا النوع من قوة المنخفضة للميكروغرام أن LSD يملك. [9] [6] في عينة من 16 شخصًا يتمتعون بصحة جيدة ، تم العثور على جرعة فموية واحدة متوسطة المدى 200 ميكروغرام من LSD لإنتاج تركيزات قصوى تبلغ 4.5 نانوغرام / مل بمتوسط ​​1.5 ساعة (نطاق 0.5-4 ساعات) بعد الإدارة. [9] [6] انخفضت تركيزات LSD بعد الخواص الحركية من الدرجة الأولى مع نصف عمر 3.6 ± 0.9 ساعة ونصف عمر نهائي قدره 8.9 ± 5.9 ساعة. [9] [6]

The effects of the dose of LSD given lasted for up to 12 hours and were closely correlated with the concentrations of LSD present in circulation over time, with no acute tolerance observed.[9][6] Only 1% of the drug was eliminated in urine unchanged, whereas 13% was eliminated as the major metabolite 2-oxo-3-hydroxy-LSD (O-H-LSD) within 24 hours.[9][6] O-H-LSD is formed by cytochrome P450 enzymes, although the specific enzymes involved are unknown, and it does not appear to be known whether O-H-LSD is pharmacologically active or not.[9][6] The oral bioavailability of LSD was crudely estimated as approximately 71% using previous data on intravenous administration of LSD.[9][6] The sample was equally divided between male and female subjects and there were no significant sex differences observed in the pharmacokinetics of LSD.[9][6]

Chemistry

The four possible stereoisomers of LSD. Only (+)-LSD is psychoactive.

LSD is a chiral compound with two stereocenters at the carbon atoms C-5 and C-8, so that theoretically four different optical isomers of LSD could exist. LSD, also called (+)-D-LSD,[citation needed] has the absolute configuration (5R,8R). The C-5 isomers of lysergamides do not exist in nature and are not formed during the synthesis from d-lysergic acid. Retrosynthetically, the C-5 stereocenter could be analysed as having the same configuration of the alpha carbon of the naturally occurring amino acid L-tryptophan, the precursor to all biosynthetic ergoline compounds.

However, LSD and iso-LSD, the two C-8 isomers, rapidly interconvert in the presence of bases, as the alpha proton is acidic and can be deprotonated and reprotonated. Non-psychoactive iso-LSD which has formed during the synthesis can be separated by chromatography and can be isomerized to LSD.

Pure salts of LSD are triboluminescent, emitting small flashes of white light when shaken in the dark.[96] LSD is strongly fluorescent and will glow bluish-white under UV light.

Synthesis

LSD is an ergoline derivative. It is commonly synthesized by reacting diethylamine with an activated form of lysergic acid. Activating reagents include phosphoryl chloride[99] and peptide coupling reagents.[90] Lysergic acid is made by alkaline hydrolysis of lysergamides like ergotamine, a substance usually derived from the ergot fungus on agar plate; or, theoretically possible, but impractical and uncommon, from ergine (lysergic acid amide, LSA) extracted from morning glory seeds.[100] Lysergic acid can also be produced synthetically, although these processes are not used in clandestine manufacture due to their low yields and high complexity.[101][102]

Dosage

White on White blotters (WoW) for sublingual administration

A single dose of LSD may be between 40 and 500 micrograms—an amount roughly equal to one-tenth the mass of a grain of sand. Threshold effects can be felt with as little as 25 micrograms of LSD.[103][104] The practice of using sub-threshold doses is called microdosing.[105] Dosages of LSD are measured in micrograms (µg), or millionths of a gram. By comparison, dosages of most drugs, both recreational and medicinal, are measured in milligrams (mg), or thousandths of a gram. For example, an active dose of mescaline, roughly 0.2 to 0.5 g, has effects comparable to 100 µg or less of LSD.[97]

In the mid-1960s, the most important black market LSD manufacturer (Owsley Stanley) distributed acid at a standard concentration of 270 µg,[106] while street samples of the 1970s contained 30 to 300 µg. By the 1980s, the amount had reduced to between 100 and 125 µg, dropping more in the 1990s to the 20–80 µg range,[107] and even more in the 2000s (decade).[106][108]

Reactivity and degradation

"LSD," writes the chemist Alexander Shulgin, "is an unusually fragile molecule ... As a salt, in water, cold, and free from air and light exposure, it is stable indefinitely."[96]

LSD has two labile protons at the tertiary stereogenic C5 and C8 positions, rendering these centers prone to epimerisation. The C8 proton is more labile due to the electron-withdrawing carboxamide attachment, but removal of the chiral proton at the C5 position (which was once also an alpha proton of the parent molecule tryptophan) is assisted by the inductively withdrawing nitrogen and pi electron delocalisation with the indole ring.[citation needed]

LSD also has enamine-type reactivity because of the electron-donating effects of the indole ring. Because of this, chlorine destroys LSD molecules on contact; even though chlorinated tap water contains only a slight amount of chlorine, the small quantity of compound typical to an LSD solution will likely be eliminated when dissolved in tap water.[96] The double bond between the 8-position and the aromatic ring, being conjugated with the indole ring, is susceptible to nucleophilic attacks by water or alcohol, especially in the presence of UV or other kinds of light. LSD often converts to "lumi-LSD," which is inactive in human beings.[96]

A controlled study was undertaken to determine the stability of LSD in pooled urine samples.[109] The concentrations of LSD in urine samples were followed over time at various temperatures, in different types of storage containers, at various exposures to different wavelengths of light, and at varying pH values. These studies demonstrated no significant loss in LSD concentration at 25 °C for up to four weeks. After four weeks of incubation, a 30% loss in LSD concentration at 37 °C and up to a 40% at 45 °C were observed. Urine fortified with LSD and stored in amber glass or nontransparent polyethylene containers showed no change in concentration under any light conditions. Stability of LSD in transparent containers under light was dependent on the distance between the light source and the samples, the wavelength of light, exposure time, and the intensity of light. After prolonged exposure to heat in alkaline pH conditions, 10 to 15% of the parent LSD epimerized to iso-LSD. Under acidic conditions, less than 5% of the LSD was converted to iso-LSD. It was also demonstrated that trace amounts of metal ions in buffer or urine could catalyze the decomposition of LSD and that this process can be avoided by the addition of EDTA.

Detection

LSD may be quantified in urine as part of a drug abuse testing program, in plasma or serum to confirm a diagnosis of poisoning in hospitalized victims or in whole blood to assist in a forensic investigation of a traffic or other criminal violation or a case of sudden death. Both the parent drug and its major metabolite are unstable in biofluids when exposed to light, heat or alkaline conditions and therefore specimens are protected from light, stored at the lowest possible temperature and analyzed quickly to minimize losses.[110]

The apparent plasma half life of LSD is considered to be around 5.1 hours with peak plasma concentrations occurring 3 hours after administration.[111]

LSD can be detected using an Ehrlich's reagent and a Hofmann's reagent.

History

... affected by a remarkable restlessness, combined with a slight dizziness. At home I lay down and sank into a not unpleasant intoxicated-like condition, characterized by an extremely stimulated imagination. In a dreamlike state, with eyes closed (I found the daylight to be unpleasantly glaring), I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors. After some two hours this condition faded away.

—Albert Hofmann, on his first experience with LSD[112]

LSD was first synthesized on November 16, 1938[113] by Swiss chemist Albert Hofmann at the Sandoz Laboratories in Basel, Switzerland as part of a large research program searching for medically useful ergot alkaloid derivatives. LSD's psychedelic properties were discovered 5 years later when Hofmann himself accidentally ingested an unknown quantity of the chemical.[114] The first intentional ingestion of LSD occurred on April 19, 1943,[115] when Hofmann ingested 250 µg of LSD. He said this would be a threshold dose based on the dosages of other ergot alkaloids. Hofmann found the effects to be much stronger than he anticipated.[116] Sandoz Laboratories introduced LSD as a psychiatric drug in 1947 and marketed LSD as a psychiatric panacea, hailing it "as a cure for everything from schizophrenia to criminal behavior, 'sexual perversions,' and alcoholism."[117] The abbreviation "LSD" is from the German "Lysergsäurediethylamid".[118]

Albert Hofmann in 2006
'Effects of Lysergic Acid Diethylamide (LSD) on Troops Marching' - 16mm film produced by the United States military circa 1958.

Beginning in the 1950s, the US Central Intelligence Agency (CIA) began a research program code named Project MKUltra. The CIA introduced LSD to the United States, purchasing the entire world's supply for $240,000 and propagating the LSD through CIA front organizations to American hospitals, clinics, prisons and research centers.[119] Experiments included administering LSD to CIA employees, military personnel, doctors, other government agents, prostitutes, mentally ill patients, and members of the general public in order to study their reactions, usually without the subjects' knowledge. The project was revealed in the US congressional Rockefeller Commission report in 1975.

In 1963, the Sandoz patents expired on LSD.[107] Several figures, including Aldous Huxley, Timothy Leary, and Al Hubbard, began to advocate the consumption of LSD. LSD became central to the counterculture of the 1960s.[120] In the early 1960s the use of LSD and other hallucinogens was advocated by new proponents of consciousness expansion such as Leary, Huxley, Alan Watts and Arthur Koestler,[121][122] and according to L. R. Veysey they profoundly influenced the thinking of the new generation of youth.[123]

On October 24, 1968, possession of LSD was made illegal in the United States.[124] The last FDA approved study of LSD in patients ended in 1980, while a study in healthy volunteers was made in the late 1980s. Legally approved and regulated psychiatric use of LSD continued in Switzerland until 1993.[125]

In November 2020, Oregon became the first US state to decriminalize possession of small amounts of LSD after voters approved Ballot Measure 110.[126]

Society and culture

Counterculture

Psychedelic art attempts to capture the visions experienced on a psychedelic trip

By the mid-1960s, the youth countercultures in California, particularly in San Francisco, had adopted the use of hallucinogenic drugs, with the first major underground LSD factory established by Owsley Stanley.[127] From 1964, the Merry Pranksters, a loose group that developed around novelist Ken Kesey, sponsored the Acid Tests, a series of events primarily staged in or near San Francisco, involving the taking of LSD (supplied by Stanley), accompanied by light shows, film projection and discordant, improvised music known as the psychedelic symphony.[128][129] The Pranksters helped popularize LSD use, through their road trips across America in a psychedelically-decorated converted school bus, which involved distributing the drug and meeting with major figures of the beat movement, and through publications about their activities such as Tom Wolfe's The Electric Kool-Aid Acid Test (1968).[130]

In San Francisco's Haight-Ashbury neighborhood, brothers Ron and Jay Thelin opened the Psychedelic Shop in January 1966.[131] The Thelins opened the store to promote safe use of LSD, which was then still legal in California. The Psychedelic Shop helped to further popularize LSD in the Haight and to make the neighborhood the unofficial capital of the hippie counterculture in the United States. Ron Thelin was also involved in organizing the Love Pageant rally, a protest held in Golden Gate park to protest California's newly adopted ban on LSD in October 1966. At the rally, hundreds of attendees took acid in unison. Although the Psychedelic Shop closed after barely a year-and-a-half in business, its role in popularizing LSD was considerable.[132]

A similar and connected nexus of LSD use in the creative arts developed around the same time in London. A key figure in this phenomenon in the UK was British academic Michael Hollingshead, who first tried LSD in America in 1961 while he was the Executive Secretary for the Institute of British-American Cultural Exchange. After being given a large quantity of pure Sandoz LSD (which was still legal at the time) and experiencing his first "trip," Hollingshead contacted Aldous Huxley, who suggested that he get in touch with Harvard academic Timothy Leary, and over the next few years, in concert with Leary and Richard Alpert, Hollingshead played a major role in their famous LSD research at Millbrook before moving to New York City, where he conducted his own LSD experiments. In 1965 Hollingshead returned to the UK and founded the World Psychedelic Center in Chelsea, London.

Music and art

In both music and art, the influence of LSD was soon being more widely seen and heard thanks to the bands that participated in the Acid Tests and related events, including the Grateful Dead, Jefferson Airplane and Big Brother and the Holding Company, and through the inventive poster and album art of San Francisco-based artists like Rick Griffin, Victor Moscoso, Bonnie MacLean, Stanley Mouse & Alton Kelley, and Wes Wilson, meant to evoke the visual experience of an LSD trip. LSD had a strong influence on the Grateful Dead and the culture of "Deadheads."[133]

Among the many famous people in the UK that Michael Hollingshead is reputed to have introduced to LSD are artist and Hipgnosis founder Storm Thorgerson, and musicians Donovan, Keith Richards, Paul McCartney, John Lennon, and George Harrison. Although establishment concern about the new drug led to it being declared an illegal drug by the Home Secretary in 1966, LSD was soon being used widely in the upper echelons of the British art and music scene, including members of the Beatles, the Rolling Stones, the Moody Blues, the Small Faces, Pink Floyd, Jimi Hendrix and others, and the products of these experiences were soon being both heard and seen by the public with singles like the Small Faces' "Itchycoo Park" and LPs like the Beatles' Sgt. Pepper's Lonely Hearts Club Band and Cream's Disraeli Gears, which featured music that showed the obvious influence of the musicians' recent psychedelic excursions, and which were packaged in elaborately-designed album covers that featured vividly-coloured psychedelic artwork by artists like Peter Blake, Martin Sharp, Hapshash and the Coloured Coat (Nigel Waymouth and Michael English) and art/music collective The Fool.

In the 1960s, musicians from psychedelic music and psychedelic rock bands began to refer (at first indirectly, and later explicitly) to the drug and attempted to recreate or reflect the experience of taking LSD in their music. A number of features are often included in psychedelic music. Exotic instrumentation, with a particular fondness for the sitar and tabla are common.[134] Electric guitars are used to create feedback, and are played through wah wah and fuzzbox effect pedals.[135] Elaborate studio effects are often used, such as backwards tapes, panning, phasing, long delay loops, and extreme reverb.[136] In the 1960s there was a use of primitive electronic instruments such as early synthesizers and the theremin.[137][138] Later forms of electronic psychedelia also employed repetitive computer-generated beats.[139] Songs allegedly referring to LSD include John Prine's "Illegal Smile" and the Beatles' song "Lucy in the Sky with Diamonds," although the authors of the latter song repeatedly denied this claim.[140][141][142]

In modern times, LSD has had a prominent influence on artists such as Keith Haring, electronic dance music, and the jam band Phish.

Legal status

The United Nations Convention on Psychotropic Substances (adopted in 1971) requires the signing parties to prohibit LSD. Hence, it is illegal in all countries that were parties to the convention, including the United States, Australia, New Zealand, and most of Europe. However, enforcement of those laws varies from country to country. Medical and scientific research with LSD in humans is permitted under the 1971 UN Convention.[143]

Australia

LSD is a Schedule 9 prohibited substance in Australia under the Poisons Standard (February 2017).[144] A Schedule 9 substance is defined as a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[144]

In Western Australia section 9 of the Misuse of Drugs Act 1981 provides for summary trial before a magistrate for possession of less than 0.004g; section 11 provides rebuttable presumptions of intent to sell or supply if the quantity is 0.002g or more, or of possession for the purpose of trafficking if 0.01g.[145]

Canada

In Canada, LSD is a controlled substance under Schedule III of the Controlled Drugs and Substances Act.[50] Every person who seeks to obtain the substance, without disclosing authorization to obtain such substances 30 days before obtaining another prescription from a practitioner, is guilty of an indictable offense and liable to imprisonment for a term not exceeding 3 years. Possession for purpose of trafficking is an indictable offense punishable by imprisonment for 10 years.

United Kingdom

In the United Kingdom, LSD is a Schedule 1 Class 'A' drug. This means it has no recognized legitimate uses and possession of the drug without a license is punishable with 7 years' imprisonment and/or an unlimited fine, and trafficking is punishable with life imprisonment and an unlimited fine (see main article on drug punishments Misuse of Drugs Act 1971).

In 2000, after consultation with members of the Royal College of Psychiatrists' Faculty of Substance Misuse, the UK Police Foundation issued the Runciman Report which recommended "the transfer of LSD from Class A to Class B."[146]

In November 2009, the UK Transform Drug Policy Foundation released in the House of Commons a guidebook to the legal regulation of drugs, After the War on Drugs: Blueprint for Regulation, which details options for regulated distribution and sale of LSD and other psychedelics.[147]

United States

LSD is Schedule I in the United States, according to the Controlled Substances Act of 1970.[148] This means LSD is illegal to manufacture, buy, possess, process, or distribute without a license from the Drug Enforcement Administration (DEA). By classifying LSD as a Schedule I substance, the DEA holds that LSD meets the following three criteria: it is deemed to have a high potential for abuse; it has no legitimate medical use in treatment; and there is a lack of accepted safety for its use under medical supervision. There are no documented deaths from chemical toxicity; most LSD deaths are a result of behavioral toxicity.[149]

There can also be substantial discrepancies between the amount of chemical LSD that one possesses and the amount of possession with which one can be charged in the US. This is because LSD is almost always present in a medium (e.g. blotter or neutral liquid), and in some contexts, the amount that can be considered with respect to sentencing is the total mass of the drug and its medium. This discrepancy was the subject of 1995 United States Supreme Court case, Neal v. United States, which determined that for finding minimum sentence lengths, the total medium weight is used, while for determining the severity of the offense, an estimation of the chemical mass is used.[150]

Lysergic acid and lysergic acid amide, LSD precursors, are both classified in Schedule III of the Controlled Substances Act.[151] Ergotamine tartrate, a precursor to lysergic acid, is regulated under the Chemical Diversion and Trafficking Act.

Personal possession of small amounts of drugs including LSD (40 units or less) was decriminalized in the U.S. state of Oregon on February 1, 2021.[152] This came as a result of the passing of 2020 Oregon Ballot Measure 110. The movement to decriminalize psychedelics in the United States includes LSD in the ongoing effort in California. In November 2020, California Senator Scott Wiener introduced a bill to decriminalize psychedelics such as psilocybin, ayahuasca, ibogaine, and LSD. In April 2021, the bill has been approved by the Senates Public Safety Committee and the Health Committee, in May 2021, it was cleared by the Senate Appropriations Committee and approved by the California Senate, and in June 2021, advanced by the Assembly Public Safety Committee.[153]

Mexico

In April 2009, the Mexican Congress approved changes in the General Health Law that decriminalized the possession of illegal drugs for immediate consumption and personal use, allowing a person to possess a moderate amount of LSD. The only restriction is that people in possession of drugs should not be within a 300-meter radius of schools, police departments, or correctional facilities. Marijuana, along with cocaine, opium, heroin, and other drugs were also decriminalized; their possession is not considered a crime as long as the dose does not exceed the limit established in the General Health Law.[154] Many[vague] question this, as cocaine is as synthesised as heroin, and both are produced as extracts from plants. The law establishes very low amount thresholds and strictly defines personal dosage. For those arrested with more than the threshold allowed by the law this can result in heavy prison sentences, as they will be assumed to be small traffickers even if there are no other indications that the amount was meant for selling.[155]

Czech Republic

In the Czech Republic, until 31 December 1998 only drug possession "for other person" (i.e. intent to sell) was criminal (apart from production, importation, exportation, offering or mediation, which was and remains criminal) while possession for personal use remained legal.[156]

On 1 January 1999, an amendment of the Criminal Code, which was necessitated in order to align the Czech drug rules with the Single Convention on Narcotic Drugs, became effective, criminalizing possession of "amount larger than small" also for personal use (Art. 187a of the Criminal Code) while possession of small amounts for personal use became a misdemeanor.[156]

The judicial practice came to the conclusion that the "amount larger than small" must be five to ten times larger (depending on drug) than a usual single dose of an average consumer.[157]

Under the Regulation No. 467/2009 Coll, possession of less than 5 doses of LSD was to be considered smaller than large for the purposes of the Criminal Code and was to be treated as a misdemeanor subject to a fine equal to a parking ticket.[158]

Ecuador

According to the 2008 Constitution of Ecuador, in its Article 364, the Ecuadorian state does not see drug consumption as a crime but only as a health concern.[159] Since June 2013 the State drugs regulatory office CONSEP has published a table which establishes maximum quantities carried by persons so as to be considered in legal possession and that person as not a seller of drugs.[159][160][161] The "CONSEP established, at their latest general meeting, that the 0.020 milligrams of LSD shall be considered the maximum consumer amount.[162]

Economics

Price

The street price of a single dose of LSD can be anywhere from $2 to $50.[163] In Europe, as of 2011, the typical cost of a dose was between €4.50 and €25.[15]

Production

Glassware seized by the DEA

An active dose of LSD is very minute, allowing a large number of doses to be synthesized from a comparatively small amount of raw material. Twenty five kilograms of precursor ergotamine tartrate can produce 5–6 kg of pure crystalline LSD; this corresponds to around 50-60 million doses at 100 µg. Because the masses involved are so small, concealing and transporting illicit LSD is much easier than smuggling cocaine, cannabis, or other illegal drugs.[164]

Manufacturing LSD requires laboratory equipment and experience in the field of organic chemistry. It takes two to three days to produce 30 to 100 grams of pure compound. It is believed that LSD is not usually produced in large quantities, but rather in a series of small batches. This technique minimizes the loss of precursor chemicals in case a step does not work as expected.[164][dead link]

Forms
Five doses of LSD, often called a "five strip"

LSD is produced in crystalline form and is then mixed with excipients or redissolved for production in ingestible forms. Liquid solution is either distributed in small vials or, more commonly, sprayed onto or soaked into a distribution medium. Historically, LSD solutions were first sold on sugar cubes, but practical considerations forced a change to tablet form. Appearing in 1968 as an orange tablet measuring about 6 mm across, "Orange Sunshine" acid was the first largely available form of LSD after its possession was made illegal. Tim Scully, a prominent chemist, made some of these tablets, but said that most "Sunshine" in the USA came by way of Ronald Stark, who imported approximately thirty-five million doses from Europe.[165]

Over a period of time, tablet dimensions, weight, shape and concentration of LSD evolved from large (4.5–8.1 mm diameter), heavyweight (≥150 mg), round, high concentration (90–350 µg/tab) dosage units to small (2.0–3.5 mm diameter) lightweight (as low as 4.7 µg/tab), variously shaped, lower concentration (12–85 µg/tab, average range 30–40 µg/tab) dosage units. LSD tablet shapes have included cylinders, cones, stars, spacecraft, and heart shapes. The smallest tablets became known as "Microdots."[166]

After tablets came "computer acid" or "blotter paper LSD," typically made by dipping a preprinted sheet of blotting paper into an LSD/water/alcohol solution.[165][166] More than 200 types of LSD tablets have been encountered since 1969 and more than 350 blotter paper designs have been observed since 1975.[166] About the same time as blotter paper LSD came "Windowpane" (AKA "Clearlight"), which contained LSD inside a thin gelatin square a quarter of an inch (6 mm) across.[165] LSD has been sold under a wide variety of often short-lived and regionally restricted street names including Acid, Trips, Uncle Sid, Blotter, Lucy, Alice and doses, as well as names that reflect the designs on the sheets of blotter paper.[48][167] Authorities have encountered the drug in other forms—including powder or crystal, and capsule.[168]

Modern distribution

LSD manufacturers and traffickers in the United States can be categorized into two groups: A few large-scale producers, and an equally limited number of small, clandestine chemists, consisting of independent producers who, operating on a comparatively limited scale, can be found throughout the country.[169][170]

As a group, independent producers are of less concern to the Drug Enforcement Administration than the large-scale groups because their product reaches only local markets.[171]

Many LSD dealers and chemists describe a religious or humanitarian purpose that motivates their illicit activity. Nicholas Schou's book Orange Sunshine: The Brotherhood of Eternal Love and Its Quest to Spread Peace, Love, and Acid to the World describes one such group, the Brotherhood of Eternal Love. The group was a major American LSD trafficking group in the late 1960s and early 1970s.[172]

In the second half of the 20th century, dealers and chemists loosely associated with the Grateful Dead like Owsley Stanley, Nicholas Sand, Karen Horning, Sarah Maltzer, "Dealer McDope," and Leonard Pickard played an essential role in distributing LSD.[133]

Mimics
LSD blotter acid mimic actually containing DOC
Different blotters which could possibly be mimics

Since 2005, law enforcement in the United States and elsewhere has seized several chemicals and combinations of chemicals in blotter paper which were sold as LSD mimics, including DOB,[173][174] a mixture of DOC and DOI,[175] 25I-NBOMe,[176] and a mixture of DOC and DOB.[177] Many mimics are toxic in comparatively small doses, or have extremely different safety profiles. Many street users of LSD are often under the impression that blotter paper which is actively hallucinogenic can only be LSD because that is the only chemical with low enough doses to fit on a small square of blotter paper. While it is true that LSD requires lower doses than most other hallucinogens, blotter paper is capable of absorbing a much larger amount of material. The DEA performed a chromatographic analysis of blotter paper containing 2C-C which showed that the paper contained a much greater concentration of the active chemical than typical LSD doses, although the exact quantity was not determined.[178] Blotter LSD mimics can have relatively small dose squares; a sample of blotter paper containing DOC seized by Concord, California police had dose markings approximately 6 mm apart.[179] Several deaths have been attributed to 25I-NBOMe.[180][181][182][183]

Research

A number of organizations—including the Beckley Foundation, MAPS, Heffter Research Institute and the Albert Hofmann Foundation—exist to fund, encourage and coordinate research into the medicinal and spiritual uses of LSD and related psychedelics.[184] New clinical LSD experiments in humans started in 2009 for the first time in 35 years.[185] As it is illegal in many areas of the world, potential medical uses are difficult to study.[41]

In 2001 the United States Drug Enforcement Administration stated that LSD "produces no aphrodisiac effects, does not increase creativity, has no lasting positive effect in treating alcoholics or criminals, does not produce a 'model psychosis', and does not generate immediate personality change."[186] More recently, experimental uses of LSD have included the treatment of alcoholism,[187] pain and cluster headache relief,[7] and prospective studies on depression.[188][189] There is evidence that psychedelics induce molecular and cellular adaptations related to neuroplasticity and that these could potentially underlie therapeutic benefits.[190]

Psychedelic therapy

In the 1950s and 1960s LSD was used in psychiatry to enhance psychotherapy known as psychedelic therapy. Some psychiatrists[who?] believed LSD was especially useful at helping patients to "unblock" repressed subconscious material through other psychotherapeutic methods,[191] and also for treating alcoholism.[192][193][194] One study concluded, "The root of the therapeutic value of the LSD experience is its potential for producing self-acceptance and self-surrender,"[195] presumably by forcing the user to face issues and problems in that individual's psyche.

Two recent reviews concluded that conclusions drawn from most of these early trials are unreliable due to serious methodological flaws. These include the absence of adequate control groups, lack of followup, and vague criteria for therapeutic outcome. In many cases studies failed to convincingly demonstrate whether the drug or the therapeutic interaction was responsible for any beneficial effects.[196][197]

In recent years organizations like the Multidisciplinary Association for Psychedelic Studies have renewed clinical research of LSD.[198]

It has been proposed that LSD be studied for use in the therapeutic setting particularly in anxiety.[199][200]

Other uses

In the 1950s and 1960s, some psychiatrists (e.g. Oscar Janiger) explored the potential effect of LSD on creativity. Experimental studies attempted to measure the effect of LSD on creative activity and aesthetic appreciation.[201][202][203][49]

Since 2008 there has been ongoing research into using LSD to alleviate anxiety for terminally ill cancer patients coping with their impending deaths.[204][205]

A 2012 meta-analysis found evidence that a single dose of LSD in conjunction with various alcoholism treatment programs was associated with a decrease in alcohol abuse, lasting for several months, but no effect was seen at one year. Adverse events included seizure, moderate confusion and agitation, nausea, vomiting, and acting in a bizarre fashion.[43]

LSD has been used as a treatment for cluster headaches with positive results in some small studies.[7]

LSD may have analgesic properties related to pain in terminally ill patients and phantom pain and may be useful for treating inflammatory diseases including rheumatoid arthritis.[206]

Notable individuals

Some notable individuals have commented publicly on their experiences with LSD.[207][208] Some of these comments date from the era when it was legally available in the US and Europe for non-medical uses, and others pertain to psychiatric treatment in the 1950s and 1960s. Still others describe experiences with illegal LSD, obtained for philosophic, artistic, therapeutic, spiritual, or recreational purposes.

  • W. H. Auden, the poet, said, "I myself have taken mescaline once and L.S.D. once. Aside from a slight schizophrenic dissociation of the I from the Not-I, including my body, nothing happened at all."[209] He also said, "LSD was a complete frost. … What it does seem to destroy is the power of communication. I have listened to tapes done by highly articulate people under LSD, for example, and they talk absolute drivel. They may have seen something interesting, but they certainly lose either the power or the wish to communicate."[210] He also said, "Nothing much happened but I did get the distinct impression that some birds were trying to communicate with me."[211]
  • Richard Feynman, a notable physicist at California Institute of Technology, tried LSD during his professorship at Caltech. Feynman largely sidestepped the issue when dictating his anecdotes; he mentions it in passing in the "O Americano, Outra Vez" section.[212][213]
  • Jerry Garcia stated in a July 3, 1989 interview for Relix Magazine, in response to the question "Have your feelings about LSD changed over the years?," "They haven't changed much. My feelings about LSD are mixed. It's something that I both fear and that I love at the same time. I never take any psychedelic, have a psychedelic experience, without having that feeling of, "I don't know what's going to happen." In that sense, it's still fundamentally an enigma and a mystery."[214]
  • Bill Gates implied in an interview with Playboy that he tried LSD during his youth.[215]
  • Aldous Huxley, author of Brave New World, became a user of psychedelics after moving to Hollywood. He was at the forefront of the counterculture's use of psychedelic drugs, which led to his 1954 work The Doors of Perception. Dying from cancer, he asked his wife on 22 November 1963 to inject him with 100 µg of LSD. He died later that day.[216]
  • Steve Jobs, co-founder and former CEO of Apple Inc., said, "Taking LSD was a profound experience, one of the most important things in my life."[217]
  • Ernst Jünger, German writer and philosopher, throughout his life had experimented with drugs such as ether, cocaine, and hashish; and later in life he used mescaline and LSD. These experiments were recorded comprehensively in Annäherungen (1970, Approaches). The novel Besuch auf Godenholm (1952, Visit to Godenholm) is clearly influenced by his early experiments with mescaline and LSD. He met with LSD inventor Albert Hofmann and they took LSD together several times. Hofmann's memoir LSD, My Problem Child describes some of these meetings.[218]
  • In a 2004 interview, Paul McCartney said that The Beatles' songs "Day Tripper" and "Lucy in the Sky with Diamonds" were inspired by LSD trips.[219] Nonetheless, John Lennon consistently stated over the course of many years that the fact that the initials of "Lucy in the Sky with Diamonds" spelled out L-S-D was a coincidence (the title came from a picture drawn by his son Julian) and that the band members did not notice until after the song had been released, and Paul McCartney corroborated that story.[220] John Lennon, George Harrison, and Ringo Starr also used the drug, although McCartney cautioned that "it's easy to overestimate the influence of drugs on the Beatles' music."[221]
  • Michel Foucault had an LSD experience with Simeon Wade in the Death Valley and later wrote “it was the greatest experience of his life, and that it profoundly changed his life and his work."[222][223] According to Wade, as soon as he came back to Paris, Foucault scrapped the second History of Sexuality's manuscript, and totally rethought the whole project.[224]
  • Kary Mullis is reported to credit LSD with helping him develop DNA amplification technology, for which he received the Nobel Prize in Chemistry in 1993.[225]
  • Oliver Sacks, a neurologist famous for writing best-selling case histories about his patients' disorders and unusual experiences, talks about his own experiences with LSD and other perception altering chemicals, in his book, Hallucinations.[226]

See also

Notes

  1. ^ From the German name Lysergsäure-diethylamid

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