<PAGE>   1
           AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON JUNE 25, 1996
                                                  REGISTRATION NO. 333-
================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                 --------------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                                 --------------

                            CYPRESS BIOSCIENCE, INC.
             (Exact name of Registrant as specified in its charter)

                DELAWARE                                    22-2389839
      (State or other jurisdiction                       (I.R.S. Employer
   of incorporation or organization)                  Identification Number)

                         4350 EXECUTIVE DRIVE, SUITE 325
                           SAN DIEGO, CALIFORNIA 92121
                                 (619) 452-2323
    (Address, including zip code, and telephone number, including area code,
                  of Registrant's principal executive offices)

                                 --------------

                           1996 EQUITY INCENTIVE PLAN

                  INCENTIVE STOCK OPTION AND APPRECIATION PLAN

                       1988 NONQUALIFIED STOCK OPTION PLAN

                             NON-PLAN STOCK OPTIONS

                            (Full title of the plans)

                                 --------------

                                 JAY D. KRANZLER
                CHIEF EXECUTIVE OFFICER, CHIEF SCIENTIFIC OFFICER
                   AND VICE CHAIRMAN OF THE BOARD OF DIRECTORS
                            CYPRESS BIOSCIENCE, INC.
                         4350 EXECUTIVE DRIVE, SUITE 325
                           SAN DIEGO, CALIFORNIA 92121
                                 (619) 452-2323
 (Name, address, including zip code, and telephone number, including area code,
                              of agent for service)

                                 --------------

                                   Copies to:

                             FREDERICK T. MUTO, ESQ.
                              CARL R. SANCHEZ, ESQ.
                              COOLEY GODWARD CASTRO
                                HUDDLESON & TATUM
                        4365 EXECUTIVE DRIVE, SUITE 1100
                               SAN DIEGO, CA 92121
                                 (619) 550-6000

                                 --------------

                         CALCULATION OF REGISTRATION FEE
<TABLE>
<CAPTION>
=========================================================================================================================
                                                                  PROPOSED           PROPOSED       
                                                                   MAXIMUM            MAXIMUM     
            TITLE OF SECURITIES                AMOUNT TO        OFFERING PRICE       AGGREGATE               AMOUNT OF
              TO BE REGISTERED               BE REGISTERED       PER SHARE(1)      OFFERING PRICE(1)     REGISTRATION FEE
- -------------------------------------------------------------------------------------------------------------------------

<S>                                          <C>                <C>                <C>                   <C>        
  Common Stock, $.02 par value                 8,806,335        $1.500 - $3.875     $17,027,707.74        $5,871.62
=========================================================================================================================
</TABLE>
<PAGE>   2
(1)  Estimated solely for the purpose of calculating the amount of the
registration fee pursuant to Rule 457. The price per share and aggregate
offering price are based upon (a) the actual exercise price for shares subject
to outstanding stock options previously granted (i) under Registrant's 1996
Equity Incentive Plan (the "1996 Plan"), (ii) under Registrant's Incentive Stock
Option and Appreciation Plan, as amended, (the "ISO Plan"), (iii) under
Registrant's Amended and Restated 1988 Nonqualified Stock Option Plan (the "1988
Plan") and (iv) outside of Registrant's 1988 Plan, ISO Plan and 1996 Plan
pursuant to Nonqualified Stock Option Agreements (the "Non-Plan Options"), and
(b) for shares issuable under the Registrant's (i) 1996 Plan and (ii) 1988 Plan
calculated on the basis of the average of the high and low sales price of
Registrant's Common Stock on June 19, 1996. The following chart shows the
calculation of the registration fee.

<TABLE>
<CAPTION>
- --------------------------------------------------------------------------------------------------------------
                                                                                                   Aggregate
              Type of Shares                   Number of Shares     Offering Price Per Share    Offering Price
- --------------------------------------------------------------------------------------------------------------
<S>                                            <C>                  <C>                         <C>          
Common Stock issuable pursuant to                 4,450,824                  $1.500              $6,676,236.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  118,333                   $1.875               $221,874.38
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  125,000                   $2.019               $252,375.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   30,000                   $2.125               $63,750.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   60,000                   $2.250               $135,000.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   75,000                   $2.438               $182,850.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  100,000                   $2.500               $250,000.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  154,500                   $1.750               $270,375.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   40,000                   $2.000               $80,000.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  225,000                   $2.125               $478,125.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   35,000                   $2.625               $91,875.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   10,000                   $3.375               $33,750.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   30,000                   $2.4375              $73,125.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   4,000                    $2.000                $8,000.00
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   10,500                   $2.625               $27,562.50
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   16,500                   $3.250               $53,625.00
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   12,000                   $3.750               $45,000.00
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   18,000                   $3.875               $69,750.00
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   60,000                   $1.500               $90,000.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   20,000                   $1.750               $35,000.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   38,000                   $1.875               $71,250.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  122,000                   $1.938               $236,436.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
</TABLE>
<PAGE>   3
<TABLE>
- --------------------------------------------------------------------------------------------------------------
<S>                                               <C>                        <C>                 <C>          
Common Stock issuable pursuant to                   8,500                    $2.000               $17,000.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  705,000                   $2.250              $1,586,250.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   65,000                   $2.125               $138,125.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   50,000                   $2.625               $131,250.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   18,605                   $2.688               $50,010.24
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   7,500                    $3.250               $24,375.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   26,230                   $3.813               $100,014.99
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   30,000                   $3.875               $116,250.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable under the 1996              2,040,843                  $2.531              $5,165,373.63
Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable under the 1988               100,000                   $2.531               $253,100.00
Plan
- --------------------------------------------------------------------------------------------------------------
</TABLE>
<PAGE>   4
                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE.

       The Company's Annual Report on Form 10-K/A for the fiscal year ended
December 31, 1995, the Company's Proxy Statement for the 1996 Annual Meeting of
Stockholders filed on March 11, 1996 pursuant to Rule 14a-6 of the Exchange Act,
the Company's Current Report on Form 8-K dated as of January 29, 1996, the
Company's Current Report on Form 8-K dated as of March 8, 1996, the Company's
Current report on Form 8-K dated as of April 1, 1996, the Company's Quarterly
Report on Form 10-Q for the quarter ended March 31, 1996, and the Company's
Registration Statement on Form S-3/A (No. 333-01071) dated May 2, 1996 filed by
the Company with the Commission are hereby incorporated by reference in this
Registration Statement except as superseded or modified herein. All documents
filed by the Company with the Commission pursuant to Section 13(a), 13(c), 14 or
15(d) of the Exchange Act after the date of this Registration Statement and
prior to the time a post-effective amendment which indicates that securities
offered have been sold or which deregisters all securities then remaining unsold
shall be deemed to be incorporated by reference into this Registration Statement
and to be a part hereof from the date of filing of such documents. Any statement
contained in any document incorporated or deemed to be incorporated by reference
herein shall be deemed to be modified or superseded for purposes of this
Registration Statement to the extent that a statement contained herein or in any
other subsequently filed document which also is or is deemed to be incorporated
by reference herein modifies or supersedes such statement. Any such statement so
modified or superseded shall not be deemed, except as modified or superseded, to
constitute a part of this Registration Statement.

ITEM 4.  DESCRIPTION OF SECURITIES.

       Not applicable.

ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

       Not applicable.

ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

       The Registrant's Certificate of Incorporation and Bylaws include
provisions to (i) eliminate the personal liability of its directors for monetary
damages resulting from breaches of their fiduciary duty to the extent permitted
by Section 102(b)(7) of the Delaware General Corporation Law (the "DGCL") and
(ii) require the Registrant to indemnify its directors and officers to the
fullest extent permitted by applicable law, including circumstances in which
indemnification is otherwise discretionary. Pursuant to Section 145 of the DGCL,
a corporation generally has the power to indemnify its present and former
directors, officers, employees and 


                                       4.
<PAGE>   5
agents against expenses incurred by them in connection with any suit to which
they are or are threatened to be made, a party by reason of their serving in
such positions so long as they acted in good faith and in a manner they
reasonably believed to be in or not opposed to, the best interests of the
corporation and with respect to any criminal action, they had no reasonable
cause to believe their conduct was unlawful. The Registrant believes that these
provisions are necessary to attract and retain qualified persons as directors
and officers. These provisions do not eliminate the directors' or officers' duty
of care, and, in appropriate circumstances, equitable remedies such as
injunctive or other forms of non-monetary relief will remain available under the
DGCL. In addition, each director will continue to be subject to liability
pursuant to Section 174 of the DGCL, for breach of the director's duty of
loyalty to the Registrant, for acts or omissions not in good faith or involving
intentional misconduct, for knowing violations of law, for acts or omissions
that the director believes to be contrary to the best interests of the
Registrant or its stockholders, for any transaction from which the director
derived an improper personal benefit, for acts or omissions involving a reckless
disregard for the director's duty to the Registrant or its stockholders when the
director was aware or should have been aware of a risk of serious injury to the
Registrant or its stockholders, for acts or omission that constitute an
unexcused pattern of inattention that amounts to an abdication of the director's
duty to the Registrant or its stockholders, for improper transactions between
the director and the Registrant and for improper loans to directors and
officers. The provision also does not affect a director's responsibilities under
any other law, such as the federal securities law or state or federal
environmental laws.

The Registrant has entered into a letter agreement with a certain former
executive officer whereby the Registrant has agreed to pay for expenses
(including attorney's fees) incurred by such executive officer in connection
with an ongoing SEC inquiry in advance of any final disposition of such inquiry.
In the event it is ultimately determined that such executive officer is not
entitled to indemnification under the terms of the Registrant's Bylaws or other
applicable laws or regulations such executive officer is obligated to repay all
amounts advanced by the Registrant on such executive officer's behalf.

The Registrant has an insurance policy covering the officers and directors of
the Registrant with respect to certain liabilities, including liabilities
arising under the Securities Act or otherwise.

ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

       Not applicable.



                                       5.
<PAGE>   6
ITEM 8.  EXHIBITS.

<TABLE>
<CAPTION>
Exhibit No.                Description
- -----------                -----------

<S>               <C>
   4.1            Registrant's Amended and Restated Certificate of Incorporation.(1)

   4.2            Registrant's Amended and Restated Bylaws.(2)

   4.3            Specimen Stock Certificate.(3)
               
   5.1            Opinion of Cooley Godward Castro Huddleson & Tatum.

   23.1           Consent of Ernst & Young LLP, Independent Auditors.

   23.2           Consent of Coopers & Lybrand L.L.P., Independent Accountants.

   23.3           Consent of Cooley Godward Castro Huddleson & Tatum.  Reference
                  is made to Exhibit 5.1.
               
   24.1           Power of Attorney.  Reference is made to page 9.

   99.1           1996 Equity Incentive Plan (the "1996 Plan").(1)

   99.2           Form of Incentive Stock Option Agreement under the 1996 Plan.(1)

   99.3           Form of Nonstatutory Stock Option Agreement under the 1996 Plan.(1)
              
   99.4           Incentive Stock Option and Appreciation Plan, as amended June 29, 1992.

   99.5           Form of Incentive Stock Option Agreement under the ISO Plan.

   99.6           Amended and Restated 1988 Nonqualified Stock Option Plan.

   99.7           Form of Nonqualified Stock Option Agreement under the 1988 Plan.

   99.8           Form of Stock Option Agreement for issuances of all Non-Plan Options.
</TABLE>

- -------------------
(1)   Filed as an exhibit to the Registrant's Form 10-Q for the quarter ended
      March 31, 1996 filed on May 15, 1996, and incorporated herein by
      reference.
             
(2)   Filed as an exhibit to the Registrant's Form 10-K for the year ended 
      December 31, 1995 filed on February 19, 1996, and incorporated herein by
      reference.

(3)   Filed as an exhibit to the Registration Statement on Form S-1 (No. 
      33-41225) and incorporated  herein by reference.


ITEM 9.  UNDERTAKINGS.

      (a)   Rule 415 Offering.

            The undersigned Registrant hereby undertakes:


                                       6.
<PAGE>   7
              (1)  To file, during any period in which offers or sales are
being made, a post-effective amendment to this Registration Statement:

                   (i)  To include any prospectus required by Section 10(a)(3) 
of the Securities Act;

                  (ii)  To reflect in the prospectus any facts or events arising
after the effective date of the Registration Statement (or the most recent
post-effective amendment thereof) which, individually or in the aggregate,
represent a fundamental change in the information set forth in the Registration
Statement. Notwithstanding the foregoing, any increase or decrease in volume of
securities offered (if the total dollar value of securities offered would not
exceed that which was registered) and any deviation from the low or high end of
the estimated maximum offering range may be reflected in the form of prospectus
filed with the Commission pursuant to Rule 424(b) (Section 230.424(b) of this
chapter) if, in the aggregate, the changes in volume and price represent no more
than a 20% change in the maximum aggregate offering price set forth in the
"Calculation of Registration Fee" table in the effective registration statement;

                 (iii)  To include any material information with respect to the
plan of distribution not previously disclosed in this Registration Statement or
any material change to such information in the Registration Statement;

              Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not
apply if this Registration Statement is on Form S-3 or Form S-8 and the
information required to be included in a post-effective amendment by those
paragraphs is contained in periodic reports filed by the Registrant pursuant to
Section 13 or Section 15(d) of the Exchange Act that are incorporated by
reference in this Registration Statement;

              (2)  That, for the purpose of determining any liability under the
Securities Act, each such post-effective amendment shall be deemed to be a new
registration statement relating to the securities offered herein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof; and

              (3)  To remove from registration by means of a post-effective
amendment any of the securities being registered which remain unsold at the
termination of the offering.

         (b)  Filings Incorporating Subsequent Exchange Act Documents By
Reference.

              The undersigned Registrant hereby undertakes that, for purposes of
determining any liability under the Securities Act, each filing of the
Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
Exchange Act (and, where applicable, each filing of an employee benefit plan's
annual report pursuant to Section 15(d) of the Exchange Act) that is
incorporated by reference in the Registration Statement shall be deemed to be a
new registration statement relating to the securities offered therein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof.


                                       7.
<PAGE>   8
         (c)  Request for Acceleration of Effective Date or Filing of
              Registration Statement on Form S-8.

              Insofar as indemnification for liabilities arising under the
Securities Act may be permitted to directors, officers and controlling persons
of the Registrant pursuant to the foregoing provisions or otherwise, the
Registrant has been advised that in the opinion of the Commission such
indemnification is against public policy as expressed in the Securities Act, and
is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the Registrant of expenses
incurred or paid by a director, officer or controlling person of the Registrant
in the successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the Registrant will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the Securities Act and will be governed by the final
adjudication of such issue.


                                       8.
<PAGE>   9
                                   SIGNATURES

      The Registrant. Pursuant to the requirements of the Securities Act of
1933, the Registrant certifies that it has reasonable grounds to believe that it
meets all of the requirements for filing on Form S-8 and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of San Diego, State of California, on June 21,
1996.

                                  CYPRESS BIOSCIENCE, INC.

                                  By /s/ JAY D. KRANZLER
                                     -------------------------------------------
                                     Jay D. Kranzler, M.D., Ph.D.
                                     Chief Executive Officer and Chief 
                                      Scientific Officer

                                POWER OF ATTORNEY

      KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature
appears below constitutes and appoints Jay D. Kranzler and Susan E. Feiner and
each of them, his true and lawful attorney-in-fact and agent, with full power of
substitution and resubstitution, for him and in his name, place and stead, in
any and all capacities, to sign any and all amendments (including post-effective
amendments) to this Registration Statement, and to file the same, with all
exhibits thereto, and other documents in connection therewith, with the
Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and
every act and thing requisite and necessary to be done in connection therewith,
as fully to all intents and purposes as he might or could do in person, hereby
ratifying and confirming all that said attorney-in-fact and agent, or any of
them, or his substitutes or substitute, may lawfully do or cause to be done by
virtue hereof.

      Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities and on the dates indicated.

<TABLE>
<S>                                      <C>                                              <C> 
/s/ JAY D. KRANZLER                      Chief Executive Officer, Chief                   June 21, 1996
- --------------------------------         Scientific Officer and Vice  
Jay D. Kranzler, M.D., Ph.D.             Chairman of the Board        
                                         (Principal Executive Officer)
                                         
/s/ SUSAN E. FEINER                      Director of Finance/Controller,                  June 21, 1996
- --------------------------------         Secretary and Treasurer                     
Susan E. Feiner                          (Principal Financial and Accounting Officer)
                                         
/s/ DEBBY JO BLANK                       President, Chief Operating
- --------------------------------         Officer and Director                             June 21, 1996
Debby Jo Blank, M.D.                                                          

/s/ RICHARD M. CROOKS                    Chairman of the Board                            June 21, 1996
- --------------------------------
Richard M. Crooks, Jr.

/s/ PHILIP J. O'REILLY                   Director                                         June 21, 1996
- --------------------------------
Philip J. O'Reilly

/s/ JACK H. VAUGHN                       Director                                         June 20, 1996
- ---------------------------------
Jack H. Vaughn
</TABLE>


                                       9.
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1
           AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON JUNE 25, 1996
                                                  REGISTRATION NO. 333-
================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                 --------------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                                 --------------

                            CYPRESS BIOSCIENCE, INC.
             (Exact name of Registrant as specified in its charter)

                DELAWARE                                    22-2389839
      (State or other jurisdiction                       (I.R.S. Employer
   of incorporation or organization)                  Identification Number)

                         4350 EXECUTIVE DRIVE, SUITE 325
                           SAN DIEGO, CALIFORNIA 92121
                                 (619) 452-2323
    (Address, including zip code, and telephone number, including area code,
                  of Registrant's principal executive offices)

                                 --------------

                           1996 EQUITY INCENTIVE PLAN

                  INCENTIVE STOCK OPTION AND APPRECIATION PLAN

                       1988 NONQUALIFIED STOCK OPTION PLAN

                             NON-PLAN STOCK OPTIONS

                            (Full title of the plans)

                                 --------------

                                 JAY D. KRANZLER
                CHIEF EXECUTIVE OFFICER, CHIEF SCIENTIFIC OFFICER
                   AND VICE CHAIRMAN OF THE BOARD OF DIRECTORS
                            CYPRESS BIOSCIENCE, INC.
                         4350 EXECUTIVE DRIVE, SUITE 325
                           SAN DIEGO, CALIFORNIA 92121
                                 (619) 452-2323
 (Name, address, including zip code, and telephone number, including area code,
                              of agent for service)

                                 --------------

                                   Copies to:

                             FREDERICK T. MUTO, ESQ.
                              CARL R. SANCHEZ, ESQ.
                              COOLEY GODWARD CASTRO
                                HUDDLESON & TATUM
                        4365 EXECUTIVE DRIVE, SUITE 1100
                               SAN DIEGO, CA 92121
                                 (619) 550-6000

                                 --------------

                         CALCULATION OF REGISTRATION FEE
=========================================================================================================================
                                                                  PROPOSED           PROPOSED       
                                                                   MAXIMUM            MAXIMUM     
            TITLE OF SECURITIES                AMOUNT TO        OFFERING PRICE       AGGREGATE               AMOUNT OF
              TO BE REGISTERED               BE REGISTERED       PER SHARE(1)      OFFERING PRICE(1)     REGISTRATION FEE
- -------------------------------------------------------------------------------------------------------------------------
Common Stock, $.02 par value                 8,806,335        $1.500 - $3.875     $17,027,707.74        $5,871.62
=========================================================================================================================
2
(1)  Estimated solely for the purpose of calculating the amount of the
registration fee pursuant to Rule 457. The price per share and aggregate
offering price are based upon (a) the actual exercise price for shares subject
to outstanding stock options previously granted (i) under Registrant's 1996
Equity Incentive Plan (the "1996 Plan"), (ii) under Registrant's Incentive Stock
Option and Appreciation Plan, as amended, (the "ISO Plan"), (iii) under
Registrant's Amended and Restated 1988 Nonqualified Stock Option Plan (the "1988
Plan") and (iv) outside of Registrant's 1988 Plan, ISO Plan and 1996 Plan
pursuant to Nonqualified Stock Option Agreements (the "Non-Plan Options"), and
(b) for shares issuable under the Registrant's (i) 1996 Plan and (ii) 1988 Plan
calculated on the basis of the average of the high and low sales price of
Registrant's Common Stock on June 19, 1996. The following chart shows the
calculation of the registration fee.
- --------------------------------------------------------------------------------------------------------------
                                                                                                   Aggregate
              Type of Shares                   Number of Shares     Offering Price Per Share    Offering Price
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                 4,450,824                  $1.500              $6,676,236.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  118,333                   $1.875               $221,874.38
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  125,000                   $2.019               $252,375.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   30,000                   $2.125               $63,750.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   60,000                   $2.250               $135,000.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   75,000                   $2.438               $182,850.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  100,000                   $2.500               $250,000.00
outstanding options under the 1996 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  154,500                   $1.750               $270,375.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   40,000                   $2.000               $80,000.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  225,000                   $2.125               $478,125.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   35,000                   $2.625               $91,875.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   10,000                   $3.375               $33,750.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   30,000                   $2.4375              $73,125.00
outstanding options under the 1988 Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   4,000                    $2.000                $8,000.00
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   10,500                   $2.625               $27,562.50
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   16,500                   $3.250               $53,625.00
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   12,000                   $3.750               $45,000.00
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   18,000                   $3.875               $69,750.00
outstanding options under the ISO Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   60,000                   $1.500               $90,000.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   20,000                   $1.750               $35,000.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   38,000                   $1.875               $71,250.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  122,000                   $1.938               $236,436.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
3

- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   8,500                    $2.000               $17,000.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                  705,000                   $2.250              $1,586,250.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   65,000                   $2.125               $138,125.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   50,000                   $2.625               $131,250.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   18,605                   $2.688               $50,010.24
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   7,500                    $3.250               $24,375.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   26,230                   $3.813               $100,014.99
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable pursuant to                   30,000                   $3.875               $116,250.00
outstanding Non-Plan Options
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable under the 1996              2,040,843                  $2.531              $5,165,373.63
Plan
- --------------------------------------------------------------------------------------------------------------
Common Stock issuable under the 1988               100,000                   $2.531               $253,100.00
Plan
- --------------------------------------------------------------------------------------------------------------
4
                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE.

       The Company's Annual Report on Form 10-K/A for the fiscal year ended
December 31, 1995, the Company's Proxy Statement for the 1996 Annual Meeting of
Stockholders filed on March 11, 1996 pursuant to Rule 14a-6 of the Exchange Act,
the Company's Current Report on Form 8-K dated as of January 29, 1996, the
Company's Current Report on Form 8-K dated as of March 8, 1996, the Company's
Current report on Form 8-K dated as of April 1, 1996, the Company's Quarterly
Report on Form 10-Q for the quarter ended March 31, 1996, and the Company's
Registration Statement on Form S-3/A (No. 333-01071) dated May 2, 1996 filed by
the Company with the Commission are hereby incorporated by reference in this
Registration Statement except as superseded or modified herein. All documents
filed by the Company with the Commission pursuant to Section 13(a), 13(c), 14 or
15(d) of the Exchange Act after the date of this Registration Statement and
prior to the time a post-effective amendment which indicates that securities
offered have been sold or which deregisters all securities then remaining unsold
shall be deemed to be incorporated by reference into this Registration Statement
and to be a part hereof from the date of filing of such documents. Any statement
contained in any document incorporated or deemed to be incorporated by reference
herein shall be deemed to be modified or superseded for purposes of this
Registration Statement to the extent that a statement contained herein or in any
other subsequently filed document which also is or is deemed to be incorporated
by reference herein modifies or supersedes such statement. Any such statement so
modified or superseded shall not be deemed, except as modified or superseded, to
constitute a part of this Registration Statement.

ITEM 4.  DESCRIPTION OF SECURITIES.

       Not applicable.

ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

       Not applicable.

ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

       The Registrant's Certificate of Incorporation and Bylaws include
provisions to (i) eliminate the personal liability of its directors for monetary
damages resulting from breaches of their fiduciary duty to the extent permitted
by Section 102(b)(7) of the Delaware General Corporation Law (the "DGCL") and
(ii) require the Registrant to indemnify its directors and officers to the
fullest extent permitted by applicable law, including circumstances in which
indemnification is otherwise discretionary. Pursuant to Section 145 of the DGCL,
a corporation generally has the power to indemnify its present and former
directors, officers, employees and 

                                       4.
5
agents against expenses incurred by them in connection with any suit to which
they are or are threatened to be made, a party by reason of their serving in
such positions so long as they acted in good faith and in a manner they
reasonably believed to be in or not opposed to, the best interests of the
corporation and with respect to any criminal action, they had no reasonable
cause to believe their conduct was unlawful. The Registrant believes that these
provisions are necessary to attract and retain qualified persons as directors
and officers. These provisions do not eliminate the directors' or officers' duty
of care, and, in appropriate circumstances, equitable remedies such as
injunctive or other forms of non-monetary relief will remain available under the
DGCL. In addition, each director will continue to be subject to liability
pursuant to Section 174 of the DGCL, for breach of the director's duty of
loyalty to the Registrant, for acts or omissions not in good faith or involving
intentional misconduct, for knowing violations of law, for acts or omissions
that the director believes to be contrary to the best interests of the
Registrant or its stockholders, for any transaction from which the director
derived an improper personal benefit, for acts or omissions involving a reckless
disregard for the director's duty to the Registrant or its stockholders when the
director was aware or should have been aware of a risk of serious injury to the
Registrant or its stockholders, for acts or omission that constitute an
unexcused pattern of inattention that amounts to an abdication of the director's
duty to the Registrant or its stockholders, for improper transactions between
the director and the Registrant and for improper loans to directors and
officers. The provision also does not affect a director's responsibilities under
any other law, such as the federal securities law or state or federal
environmental laws.

The Registrant has entered into a letter agreement with a certain former
executive officer whereby the Registrant has agreed to pay for expenses
(including attorney's fees) incurred by such executive officer in connection
with an ongoing SEC inquiry in advance of any final disposition of such inquiry.
In the event it is ultimately determined that such executive officer is not
entitled to indemnification under the terms of the Registrant's Bylaws or other
applicable laws or regulations such executive officer is obligated to repay all
amounts advanced by the Registrant on such executive officer's behalf.

The Registrant has an insurance policy covering the officers and directors of
the Registrant with respect to certain liabilities, including liabilities
arising under the Securities Act or otherwise.

ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

       Not applicable.

                                       5.
6
ITEM 8.  EXHIBITS.
Exhibit No.                Description
- -----------                -----------
4.1            Registrant's Amended and Restated Certificate of Incorporation.(1)

   4.2            Registrant's Amended and Restated Bylaws.(2)

   4.3            Specimen Stock Certificate.(3)
               
   5.1            Opinion of Cooley Godward Castro Huddleson & Tatum.

   23.1           Consent of Ernst & Young LLP, Independent Auditors.

   23.2           Consent of Coopers & Lybrand L.L.P., Independent Accountants.

   23.3           Consent of Cooley Godward Castro Huddleson & Tatum.  Reference
                  is made to Exhibit 5.1.
               
   24.1           Power of Attorney.  Reference is made to page 9.

   99.1           1996 Equity Incentive Plan (the "1996 Plan").(1)

   99.2           Form of Incentive Stock Option Agreement under the 1996 Plan.(1)

   99.3           Form of Nonstatutory Stock Option Agreement under the 1996 Plan.(1)
              
   99.4           Incentive Stock Option and Appreciation Plan, as amended June 29, 1992.

   99.5           Form of Incentive Stock Option Agreement under the ISO Plan.

   99.6           Amended and Restated 1988 Nonqualified Stock Option Plan.

   99.7           Form of Nonqualified Stock Option Agreement under the 1988 Plan.

   99.8           Form of Stock Option Agreement for issuances of all Non-Plan Options.
- -------------------
(1)   Filed as an exhibit to the Registrant's Form 10-Q for the quarter ended
      March 31, 1996 filed on May 15, 1996, and incorporated herein by
      reference.
             
(2)   Filed as an exhibit to the Registrant's Form 10-K for the year ended 
      December 31, 1995 filed on February 19, 1996, and incorporated herein by
      reference.

(3)   Filed as an exhibit to the Registration Statement on Form S-1 (No. 
      33-41225) and incorporated  herein by reference.

ITEM 9.  UNDERTAKINGS.

      (a)   Rule 415 Offering.

            The undersigned Registrant hereby undertakes:

                                       6.
7
              (1)  To file, during any period in which offers or sales are
being made, a post-effective amendment to this Registration Statement:

                   (i)  To include any prospectus required by Section 10(a)(3) 
of the Securities Act;

                  (ii)  To reflect in the prospectus any facts or events arising
after the effective date of the Registration Statement (or the most recent
post-effective amendment thereof) which, individually or in the aggregate,
represent a fundamental change in the information set forth in the Registration
Statement. Notwithstanding the foregoing, any increase or decrease in volume of
securities offered (if the total dollar value of securities offered would not
exceed that which was registered) and any deviation from the low or high end of
the estimated maximum offering range may be reflected in the form of prospectus
filed with the Commission pursuant to Rule 424(b) (Section 230.424(b) of this
chapter) if, in the aggregate, the changes in volume and price represent no more
than a 20% change in the maximum aggregate offering price set forth in the
"Calculation of Registration Fee" table in the effective registration statement;

                 (iii)  To include any material information with respect to the
plan of distribution not previously disclosed in this Registration Statement or
any material change to such information in the Registration Statement;

              Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not
apply if this Registration Statement is on Form S-3 or Form S-8 and the
information required to be included in a post-effective amendment by those
paragraphs is contained in periodic reports filed by the Registrant pursuant to
Section 13 or Section 15(d) of the Exchange Act that are incorporated by
reference in this Registration Statement;

              (2)  That, for the purpose of determining any liability under the
Securities Act, each such post-effective amendment shall be deemed to be a new
registration statement relating to the securities offered herein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof; and

              (3)  To remove from registration by means of a post-effective
amendment any of the securities being registered which remain unsold at the
termination of the offering.

         (b)  Filings Incorporating Subsequent Exchange Act Documents By
Reference.

              The undersigned Registrant hereby undertakes that, for purposes of
determining any liability under the Securities Act, each filing of the
Registrant's annual report pursuant to Section 13(a) or Section 15(d) of the
Exchange Act (and, where applicable, each filing of an employee benefit plan's
annual report pursuant to Section 15(d) of the Exchange Act) that is
incorporated by reference in the Registration Statement shall be deemed to be a
new registration statement relating to the securities offered therein, and the
offering of such securities at that time shall be deemed to be the initial bona
fide offering thereof.

                                       7.
8
         (c)  Request for Acceleration of Effective Date or Filing of
              Registration Statement on Form S-8.

              Insofar as indemnification for liabilities arising under the
Securities Act may be permitted to directors, officers and controlling persons
of the Registrant pursuant to the foregoing provisions or otherwise, the
Registrant has been advised that in the opinion of the Commission such
indemnification is against public policy as expressed in the Securities Act, and
is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the Registrant of expenses
incurred or paid by a director, officer or controlling person of the Registrant
in the successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the Registrant will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the Securities Act and will be governed by the final
adjudication of such issue.

                                       8.
9
                                   SIGNATURES

      The Registrant. Pursuant to the requirements of the Securities Act of
1933, the Registrant certifies that it has reasonable grounds to believe that it
meets all of the requirements for filing on Form S-8 and has duly caused this
Registration Statement to be signed on its behalf by the undersigned, thereunto
duly authorized, in the City of San Diego, State of California, on June 21,
1996.

                                  CYPRESS BIOSCIENCE, INC.

                                  By /s/ JAY D. KRANZLER
                                     -------------------------------------------
                                     Jay D. Kranzler, M.D., Ph.D.
                                     Chief Executive Officer and Chief 
                                      Scientific Officer

                                POWER OF ATTORNEY

      KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature
appears below constitutes and appoints Jay D. Kranzler and Susan E. Feiner and
each of them, his true and lawful attorney-in-fact and agent, with full power of
substitution and resubstitution, for him and in his name, place and stead, in
any and all capacities, to sign any and all amendments (including post-effective
amendments) to this Registration Statement, and to file the same, with all
exhibits thereto, and other documents in connection therewith, with the
Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and
every act and thing requisite and necessary to be done in connection therewith,
as fully to all intents and purposes as he might or could do in person, hereby
ratifying and confirming all that said attorney-in-fact and agent, or any of
them, or his substitutes or substitute, may lawfully do or cause to be done by
virtue hereof.

      Pursuant to the requirements of the Securities Act of 1933, this
Registration Statement has been signed by the following persons in the
capacities and on the dates indicated.
/s/ JAY D. KRANZLER                      Chief Executive Officer, Chief                   June 21, 1996
- --------------------------------         Scientific Officer and Vice  
Jay D. Kranzler, M.D., Ph.D.             Chairman of the Board        
                                         (Principal Executive Officer)
                                         
/s/ SUSAN E. FEINER                      Director of Finance/Controller,                  June 21, 1996
- --------------------------------         Secretary and Treasurer                     
Susan E. Feiner                          (Principal Financial and Accounting Officer)
                                         
/s/ DEBBY JO BLANK                       President, Chief Operating
- --------------------------------         Officer and Director                             June 21, 1996
Debby Jo Blank, M.D.                                                          

/s/ RICHARD M. CROOKS                    Chairman of the Board                            June 21, 1996
- --------------------------------
Richard M. Crooks, Jr.

/s/ PHILIP J. O'REILLY                   Director                                         June 21, 1996
- --------------------------------
Philip J. O'Reilly

/s/ JACK H. VAUGHN                       Director                                         June 20, 1996
- ---------------------------------
Jack H. Vaughn
9.